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Sample records for dynamic signal analyses

  1. Genetic Analyses of Integrin Signaling

    PubMed Central

    Wickström, Sara A.; Radovanac, Korana; Fässler, Reinhard

    2011-01-01

    The development of multicellular organisms, as well as maintenance of organ architecture and function, requires robust regulation of cell fates. This is in part achieved by conserved signaling pathways through which cells process extracellular information and translate this information into changes in proliferation, differentiation, migration, and cell shape. Gene deletion studies in higher eukaryotes have assigned critical roles for components of the extracellular matrix (ECM) and their cellular receptors in a vast number of developmental processes, indicating that a large proportion of this signaling is regulated by cell-ECM interactions. In addition, genetic alterations in components of this signaling axis play causative roles in several human diseases. This review will discuss what genetic analyses in mice and lower organisms have taught us about adhesion signaling in development and disease. PMID:21421914

  2. Nonlinear structural crash dynamics analyses

    NASA Technical Reports Server (NTRS)

    Hayduk, R. J.; Thomson, R. G.; Wittlin, G.; Kamat, M. P.

    1979-01-01

    Presented in this paper are the results of three nonlinear computer programs, KRASH, ACTION and DYCAST used to analyze the dynamic response of a twin-engine, low-wing airplane section subjected to a 8.38 m/s (27.5 ft/s) vertical impact velocity crash condition. This impact condition simulates the vertical sink rate in a shallow aircraft landing or takeoff accident. The three distinct analysis techniques for nonlinear dynamic response of aircraft structures are briefly examined and compared versus each other and the experimental data. The report contains brief descriptions of the three computer programs, the respective aircraft section mathematical models, pertinent data from the experimental test performed at NASA Langley, and a comparison of the analyses versus test results. Cost and accuracy comparisons between the three analyses are made to illustrate the possible uses of the different nonlinear programs and their future potential.

  3. Wavelet-Based Multiresolution Analyses of Signals

    DTIC Science & Technology

    1992-06-01

    classification. Some signals, notably those of a transient nature, are inherently difficult to analyze with these traditional tools. The Discrete Wavelet Transform has...scales. This thesis investigates dyadic discrete wavelet decompositions of signals. A new multiphase wavelet transform is proposed and investigated. The

  4. Dynamics in atomic signaling games.

    PubMed

    Fox, Michael J; Touri, Behrouz; Shamma, Jeff S

    2015-07-07

    We study an atomic signaling game under stochastic evolutionary dynamics. There are a finite number of players who repeatedly update from a finite number of available languages/signaling strategies. Players imitate the most fit agents with high probability or mutate with low probability. We analyze the long-run distribution of states and show that, for sufficiently small mutation probability, its support is limited to efficient communication systems. We find that this behavior is insensitive to the particular choice of evolutionary dynamic, a property that is due to the game having a potential structure with a potential function corresponding to average fitness. Consequently, the model supports conclusions similar to those found in the literature on language competition. That is, we show that efficient languages eventually predominate the society while reproducing the empirical phenomenon of linguistic drift. The emergence of efficiency in the atomic case can be contrasted with results for non-atomic signaling games that establish the non-negligible possibility of convergence, under replicator dynamics, to states of unbounded efficiency loss.

  5. Signal Transduction Pathways of TNAP: Molecular Network Analyses.

    PubMed

    Négyessy, László; Györffy, Balázs; Hanics, János; Bányai, Mihály; Fonta, Caroline; Bazsó, Fülöp

    2015-01-01

    Despite the growing body of evidence pointing on the involvement of tissue non-specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy and Alzheimer's disease, our understanding about the role of TNAP in the regulation of neurotransmission is severely limited. The aim of our study was to integrate the fragmented knowledge into a comprehensive view regarding neuronal functions of TNAP using objective tools. As a model we used the signal transduction molecular network of a pyramidal neuron after complementing with TNAP related data and performed the analysis using graph theoretic tools. The analyses show that TNAP is in the crossroad of numerous pathways and therefore is one of the key players of the neuronal signal transduction network. Through many of its connections, most notably with molecules of the purinergic system, TNAP serves as a controller by funnelling signal flow towards a subset of molecules. TNAP also appears as the source of signal to be spread via interactions with molecules involved among others in neurodegeneration. Cluster analyses identified TNAP as part of the second messenger signalling cascade. However, TNAP also forms connections with other functional groups involved in neuronal signal transduction. The results indicate the distinct ways of involvement of TNAP in multiple neuronal functions and diseases.

  6. Static and dynamic analyses of tensegrity structures

    NASA Astrophysics Data System (ADS)

    Nishimura, Yoshitaka

    Tensegrity structures are a class of truss structures consisting of a continuous set of tension members (cables) and a discrete set of compression members (bars). Since tensegrity structures are light weight and can be compactly stowed and deployed, cylindrical tensegrity modules have been proposed for space structures. From a view point of structural dynamics, tensegrity structures pose a new set of problems, i.e., initial shape finding. Initial configurations of tensegrity structures must be computed by imposing a pre-stressability condition to initial equilibrium equations. There are ample qualitative statements regarding the initial geometry of cylindrical and spherical tensegrity modules. Quantitative initial shape anlyses have only been performed on one-stage and two-stage cylindrical modules. However, analytical expressions for important geometrical parameters such as twist angles and overlap ratios lack the definition of the initial shape of both cylindrical and spherical tensegrity modules. In response to the above needs, a set of static and dynamic characterization procedures for tensegrity modules was first developed. The procedures were subsequently applied to Buckminster Fuller's spherical tensegrity modules. Both the initial shape and the corresponding pre-stress mode were analytically obtained by using the graphs of the tetrahedral, octahedral (cubic), and icosahedral (dodecahedral) groups. For pre-stressed configurations, modal analyses were conducted to classify a large number of infinitesimal mechanism modes. The procedures also applied tocyclic cylindrical tensegrity modules with an arbitrary number of stages. It was found that both the Maxwell number and the number of infinitesimal mechanism modes are independent of the number of stages in the axial direction. A reduced set of equilibrium equations was derived by incorporating cyclic symmetry and the flip, or quasi-flip, symmetry of the cylindrical modules. For multi-stage modules with more than

  7. Optimal temporal patterns for dynamical cellular signaling

    NASA Astrophysics Data System (ADS)

    Hasegawa, Yoshihiko

    2016-11-01

    Cells use temporal dynamical patterns to transmit information via signaling pathways. As optimality with respect to the environment plays a fundamental role in biological systems, organisms have evolved optimal ways to transmit information. Here, we use optimal control theory to obtain the dynamical signal patterns for the optimal transmission of information, in terms of efficiency (low energy) and reliability (low uncertainty). Adopting an activation-deactivation decoding network, we reproduce several dynamical patterns found in actual signals, such as steep, gradual, and overshooting dynamics. Notably, when minimizing the energy of the input signal, the optimal signals exhibit overshooting, which is a biphasic pattern with transient and steady phases; this pattern is prevalent in actual dynamical patterns. We also identify conditions in which these three patterns (steep, gradual, and overshooting) confer advantages. Our study shows that cellular signal transduction is governed by the principle of minimizing free energy dissipation and uncertainty; these constraints serve as selective pressures when designing dynamical signaling patterns.

  8. Time-frequency Analyses of AE Signals in YBCO Superconductors

    NASA Astrophysics Data System (ADS)

    Nanato, N.; Takemoto, N.

    AE (Acoustic Emission) measurements are well known methods to detect mechanical signals from superconducting coil The mechanical signals could be generated by micro cracks of epoxy resins, the motion of superconductors and the thermal expansion of superconductors, which were generated before and/or after a quench. We have presented a time-frequency visualization of AE signals as a method to detect the quench. We can detect very small AE signals regardless of lectromagnetic noises and can find the time of the AE occurrence and the frequency bands of AE signals by using this method. Recently it has been presented that YBCO superconductors are delaminated and degraded by a transverse tensile stress. The delamination is accompanied with AE signals. Also, it is known that amplitudes and frequency bands of AE signals vary with causes of AE occurrence. In this paper, we present time-frequency analyses of AE signa s caused by the delamination of a YBCO superconductor and the micro of epoxy resins.

  9. Analyses and Measures of GPR Signal with Superimposed Noise

    NASA Astrophysics Data System (ADS)

    Chicarella, Simone; Ferrara, Vincenzo; D'Atanasio, Paolo; Frezza, Fabrizio; Pajewski, Lara; Pavoncello, Settimio; Prontera, Santo; Tedeschi, Nicola; Zambotti, Alessandro

    2014-05-01

    The influence of EM noises and environmental hard conditions on the GPR surveys has been examined analytically [1]. In the case of pulse radar GPR, many unwanted signals as stationary clutter, non-stationary clutter, random noise, and time jitter, influence the measurement signal. When GPR is motionless, stationary clutter is the most dominant signal component due to the reflections of static objects different from the investigated target, and to the direct antenna coupling. Moving objects like e.g. persons and vehicles, and the swaying of tree crown, produce non-stationary clutter. Device internal noise and narrowband jamming are e.g. two potential sources of random noises. Finally, trigger instabilities generate random jitter. In order to estimate the effective influence of these noise signal components, we organized some experimental setup of measurement. At first, we evaluated for the case of a GPR basic detection, simpler image processing of radargram. In the future, we foresee experimental measurements for detection of the Doppler frequency changes induced by movements of targets (like physiological movements of survivors under debris). We obtain image processing of radargram by using of GSSI SIR® 2000 GPR system together with the UWB UHF GPR-antenna (SUB-ECHO HBD 300, a model manufactured by Radarteam company). Our work includes both characterization of GPR signal without (or almost without) a superimposed noise, and the effect of jamming originated from the coexistence of a different radio signal. For characterizing GPR signal, we organized a measurement setup that includes the following instruments: mod. FSP 30 spectrum analyser by Rohde & Schwarz which operates in the frequency range 9 KHz - 30 GHz, mod. Sucoflex 104 cable by Huber Suhner (10 MHz - 18 GHz), and HL050 antenna by Rohde & Schwarz (bandwidth: from 850 MHz to 26.5 GHz). The next analysis of superimposed jamming will examine two different signal sources: by a cellular phone and by a

  10. Dynamic Analyses Including Joints Of Truss Structures

    NASA Technical Reports Server (NTRS)

    Belvin, W. Keith

    1991-01-01

    Method for mathematically modeling joints to assess influences of joints on dynamic response of truss structures developed in study. Only structures with low-frequency oscillations considered; only Coulomb friction and viscous damping included in analysis. Focus of effort to obtain finite-element mathematical models of joints exhibiting load-vs.-deflection behavior similar to measured load-vs.-deflection behavior of real joints. Experiments performed to determine stiffness and damping nonlinearities typical of joint hardware. Algorithm for computing coefficients of analytical joint models based on test data developed to enable study of linear and nonlinear effects of joints on global structural response. Besides intended application to large space structures, applications in nonaerospace community include ground-based antennas and earthquake-resistant steel-framed buildings.

  11. Two complementary paradigms for analysing population dynamics.

    PubMed Central

    Krebs, Charles J

    2002-01-01

    To understand why population growth rate is sometimes positive and sometimes negative, ecologists have adopted two main approaches. The most common approach is through the density paradigm by plotting population growth rate against population density. The second approach is through the mechanistic paradigm by plotting population growth rate against the relevant ecological processes affecting the population. The density paradigm is applied a posteriori, works sometimes but not always and is remarkably useless in solving management problems or in providing an understanding of why populations change in size. The mechanistic paradigm investigates the factors that supposedly drive density changes and is identical to Caughley's declining population paradigm of conservation biology. The assumption that we can uncover invariant relationships between population growth rate and some other variables is an article of faith. Numerous commercial fishery applications have failed to find the invariant relationships between stock and recruitment that are predicted by the density paradigm. Environmental variation is the rule, and non-equilibrial dynamics should force us to look for the mechanisms of population change. If multiple factors determine changes in population density, there can be no predictability in either of these paradigms and we will become environmental historians rather than scientists with useful generalizations for the population problems of this century. Defining our questions clearly and adopting an experimental approach with crisp alternative hypotheses and adequate controls will be essential to building useful generalizations for solving the practical problems of population management in fisheries, wildlife and conservation. PMID:12396513

  12. Dynamic behaviour of a rolling tyre: Experimental and numerical analyses

    NASA Astrophysics Data System (ADS)

    Gonzalez Diaz, Cristobal; Kindt, Peter; Middelberg, Jason; Vercammen, Stijn; Thiry, Christophe; Close, Roland; Leyssens, Jan

    2016-03-01

    Based on the results of experimental and numerical analyses, the effect of rotation on the tyre dynamic behaviour is investigated. Better understanding of these effects will further improve the ability to control and optimize the noise and vibrations that result from the interaction between the road surface and the rolling tyre. Therefore, more understanding in the complex tyre dynamic properties will contribute to develop tyre design strategies to lower the tyre/road noise while less affecting other tyre performances. The presented work is performed in the framework of the European industry-academia project TIRE-DYN, with partners Goodyear, Katholieke Universiteit Leuven and LMS International. The effect of rotation on the tyre dynamic behaviour is quantified for different operating conditions of the tyre, such as load, air pressure and rotation speed. By means of experimental and numerical analyses, the effects of rotation on the tyre dynamic behaviour are studied.

  13. Dynamic Redox Regulation of IL-4 Signaling

    PubMed Central

    Dwivedi, Gaurav; Gran, Margaret A.; Bagchi, Pritha; Kemp, Melissa L.

    2015-01-01

    Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation. PMID:26562652

  14. Comprehensive Logic Based Analyses of Toll-Like Receptor 4 Signal Transduction Pathway

    PubMed Central

    Padwal, Mahesh Kumar; Sarma, Uddipan; Saha, Bhaskar

    2014-01-01

    Among the 13 TLRs in the vertebrate systems, only TLR4 utilizes both Myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adapter interferon-β-inducing Factor (TRIF) adaptors to transduce signals triggering host-protective immune responses. Earlier studies on the pathway combined various experimental data in the form of one comprehensive map of TLR signaling. But in the absence of adequate kinetic parameters quantitative mathematical models that reveal emerging systems level properties and dynamic inter-regulation among the kinases/phosphatases of the TLR4 network are not yet available. So, here we used reaction stoichiometry-based and parameter independent logical modeling formalism to build the TLR4 signaling network model that captured the feedback regulations, interdependencies between signaling kinases and phosphatases and the outcome of simulated infections. The analyses of the TLR4 signaling network revealed 360 feedback loops, 157 negative and 203 positive; of which, 334 loops had the phosphatase PP1 as an essential component. The network elements' interdependency (positive or negative dependencies) in perturbation conditions such as the phosphatase knockout conditions revealed interdependencies between the dual-specific phosphatases MKP-1 and MKP-3 and the kinases in MAPK modules and the role of PP2A in the auto-regulation of Calmodulin kinase-II. Our simulations under the specific kinase or phosphatase gene-deficiency or inhibition conditions corroborated with several previously reported experimental data. The simulations to mimic Yersinia pestis and E. coli infections identified the key perturbation in the network and potential drug targets. Thus, our analyses of TLR4 signaling highlights the role of phosphatases as key regulatory factors in determining the global interdependencies among the network elements; uncovers novel signaling connections; identifies potential drug targets for infections. PMID:24699232

  15. Microwave signal processing with photorefractive dynamic holography

    NASA Astrophysics Data System (ADS)

    Fotheringham, Edeline B.

    Have you ever found yourself listening to the music playing from the closest stereo rather than to the bromidic (uninspiring) person speaking to you? Your ears receive information from two sources but your brain listens to only one. What if your cell phone could distinguish among signals sharing the same bandwidth too? There would be no "full" channels to stop you from placing or receiving a call. This thesis presents a nonlinear optical circuit capable of distinguishing uncorrelated signals that have overlapping temporal bandwidths. This so called autotuning filter is the size of a U.S. quarter dollar and requires less than 3 mW of optical power to operate. It is basically an oscillator in which the losses are compensated with dynamic holographic gain. The combination of two photorefractive crystals in the resonator governs the filter's winner-take-all dynamics through signal-competition for gain. This physical circuit extracts what is mathematically referred to as the largest principal component of its spatio-temporal input space. The circuit's practicality is demonstrated by its incorporation in an RF-photonic system. An unknown mixture of unknown microwave signals, received by an antenna array, constitutes the input to the system. The output electronically returns one of the original microwave signals. The front-end of the system down converts the 10 GHz microwave signals and amplifies them before the signals phase modulate optical beams. The optical carrier is suppressed from these beams so that it may not be considered as a signal itself to the autotuning filter. The suppression is achieved with two-beam coupling in a single photorefractive crystal. The filter extracts the more intense of the signals present on the carrier-suppressed input beams. The detection of the extracted signal restores the microwave signal to an electronic form. The system, without the receiving antenna array, is packaged in a 13 x 18 x 6″ briefcase. Its power consumption equals that

  16. Pattern Selection by Dynamical Biochemical Signals

    PubMed Central

    Palau-Ortin, David; Formosa-Jordan, Pau; Sancho, José M.; Ibañes, Marta

    2015-01-01

    The development of multicellular organisms involves cells to decide their fate upon the action of biochemical signals. This decision is often spatiotemporally coordinated such that a spatial pattern arises. The dynamics that drive pattern formation usually involve genetic nonlinear interactions and positive feedback loops. These complex dynamics may enable multiple stable patterns for the same conditions. Under these circumstances, pattern formation in a developing tissue involves a selection process: why is a certain pattern formed and not another stable one? Herein we computationally address this issue in the context of the Notch signaling pathway. We characterize a dynamical mechanism for developmental selection of a specific pattern through spatiotemporal changes of the control parameters of the dynamics, in contrast to commonly studied situations in which initial conditions and noise determine which pattern is selected among multiple stable ones. This mechanism can be understood as a path along the parameter space driven by a sequence of biochemical signals. We characterize the selection process for three different scenarios of this dynamical mechanism that can take place during development: the signal either 1) acts in all the cells at the same time, 2) acts only within a cluster of cells, or 3) propagates along the tissue. We found that key elements for pattern selection are the destabilization of the initial pattern, the subsequent exploration of other patterns determined by the spatiotemporal symmetry of the parameter changes, and the speeds of the path compared to the timescales of the pattern formation process itself. Each scenario enables the selection of different types of patterns and creates these elements in distinct ways, resulting in different features. Our approach extends the concept of selection involved in cellular decision-making, usually applied to cell-autonomous decisions, to systems that collectively make decisions through cell

  17. Decoding dynamic Ca2+ signaling in the vascular endothelium

    PubMed Central

    Taylor, Mark S.; Francis, Michael

    2014-01-01

    Although acute and chronic vasoregulation is inherently driven by endothelial Ca2+, control and targeting of Ca2+-dependent signals are poorly understood. Recent studies have revealed localized and dynamic endothelial Ca2+ events comprising an intricate signaling network along the vascular intima. Discrete Ca2+ transients emerging from both internal stores and plasmalemmal cation channels couple to specific membrane K+ channels, promoting endothelial hyperpolarization and vasodilation. The spatiotemporal tuning of these signals, rather than global Ca2+ elevation, appear to direct endothelial functions under physiologic conditions. In fact, altered patterns of dynamic Ca2+ signaling may underlie essential endothelial dysfunction in a variety of cardiovascular diseases. Advances in imaging approaches and analyses in recent years have allowed for detailed detection, quantification, and evaluation of Ca2+ dynamics in intact endothelium. Here, we discuss recent insights into these signals, including their sources of origination and their functional encoding. We also address key aspects of data acquisition and interpretation, including broad applications of automated high-content analysis. PMID:25452732

  18. Dynamic Failure of Materials. Volume 1 - Experiments and Analyses

    DTIC Science & Technology

    1998-11-01

    methods , constitutive modeling approaches, and numerical computation approaches and results. We hope this work will be useful to investigators and...INTRODUCTION 1 1.1 HISTORICAL BACKGROUND 1 1.2 DYNAMIC FAILURE PROCESS 4 1.3 EXPERIMENTAL METHODS AND ANALYSES 14 1.4 CONSTITUTIVE RELATIONS FOR...WAVES 61 3.5 ELASTIC-PLASTIC RESPONSE 65 3.6 COMPUTER SIMULATION METHODS 73 3.6.1 Requirements for Constitutive Relations 74 TABLE OF

  19. Thermal, dynamic mechanical, and dielectric analyses of some polyurethane biocomposites.

    PubMed

    Macocinschi, Doina; Filip, Daniela; Vlad, Stelian; Cristea, Mariana; Musteata, Valentina; Ibanescu, Sorin

    2012-08-01

    Polymer biocomposites based on segmented poly(ester urethane) and extracellular matrix components have been prepared for the development of tissue engineering applications with improved biological characteristics of the materials in contact with blood and tissues for long periods. Thermal, dynamical, and dielectrical analyses were employed to study the molecular dynamics of these materials and the influence of changing the physical network morphology and hydrogen bond interactions accompanied by phase transitions, interfacial effects, and polarization or conductivity. All phenomena that concur in the tested materials are evaluated by cross-examination of the dynamic mechanical characteristic properties (storage modulus, loss modulus, and loss factor) and dielectric properties (relative permittivity, relative loss factor, and loss tangent) as a function of temperature. Comparative aspects were elucidated by calculating the apparent activation energies of multiplex experiments.

  20. Preliminary Analyses of Beidou Signal-In Anomaly Since 2013

    NASA Astrophysics Data System (ADS)

    Wu, Y.; Ren, J.; Liu, W.

    2016-06-01

    As BeiDou navigation system has been operational since December 2012. There is an increasing desire to use multiple constellation to improve positioning performance. The signal-in-space (SIS) anomaly caused by the ground control and the space vehicle is one of the major threats to affect the integrity. For a young Global Navigation Satellite System, knowledge about SIS anomalies in history is very important for not only assessing the SIS integrity performance of a constellation but also providing the assumption for ARAIM (Advanced Receiver Autonomous Integrity Monitoring). In this paper, the broadcast ephemerides and the precise ones are pre-processed for avoiding the false anomaly identification. The SIS errors over the period of Mar. 2013-Feb. 2016 are computed by comparing the broadcast ephemerides with the precise ones. The time offsets between GPST (GPS time) and BDT (BeiDou time) are estimated and removed by an improved estimation algorithm. SIS worst-UREs are computed and a RMS criteria are investigated to identify the SIS anomalies. The results show that the probability of BeiDou SIS anomalies is in 10-3 level in last three years. Even though BeiDou SIS integrity performance currently cannot match the GPS integrity performances, the result indicates that BeiDou has a tendency to improve its integrity performance.

  1. Noise reduction by dynamic signal preemphasis

    NASA Astrophysics Data System (ADS)

    Takeda, Kazuyuki; Takegoshi, K.

    2011-02-01

    In this work we propose an approach to reduce the digitization noise for a given dynamic range, i.e., the number of bits, of an analog to digital converter used in an NMR receiver. In this approach, the receiver gain is dynamically increased so that the free induction decay is recorded in such an emphasized way that the decaying signal is digitized using as many number of bits as possible, and at the stage of data processing, the original signal profile is restored by applying the apodization that compensates the effect of the preemphasis. This approach, which we call APodization after Receiver gain InCrement during Ongoing sequence with Time (APRICOT), is performed in a solid-state system containing a pair of 13C spins, one of which is fully isotopically labeled and the other is naturally abundant. It is demonstrated that the exceedingly smaller peak buried in the digitization noise in the conventional approach can be revealed by employing APRICOT.

  2. Perspective: Dynamics of receptor tyrosine kinase signaling complexes.

    PubMed

    Mayer, Bruce J

    2012-08-14

    Textbook descriptions of signal transduction complexes provide a static snapshot view of highly dynamic events. Despite enormous strides in identifying the key components of signaling complexes and the underlying mechanisms of signal transduction, our understanding of the dynamic behavior of these complexes has lagged behind. Using the example of receptor tyrosine kinases, this perspective takes a fresh look at the dynamics of the system and their potential impact on signal processing.

  3. Analysing connectivity with Granger causality and dynamic causal modelling.

    PubMed

    Friston, Karl; Moran, Rosalyn; Seth, Anil K

    2013-04-01

    This review considers state-of-the-art analyses of functional integration in neuronal macrocircuits. We focus on detecting and estimating directed connectivity in neuronal networks using Granger causality (GC) and dynamic causal modelling (DCM). These approaches are considered in the context of functional segregation and integration and--within functional integration--the distinction between functional and effective connectivity. We review recent developments that have enjoyed a rapid uptake in the discovery and quantification of functional brain architectures. GC and DCM have distinct and complementary ambitions that are usefully considered in relation to the detection of functional connectivity and the identification of models of effective connectivity. We highlight the basic ideas upon which they are grounded, provide a comparative evaluation and point to some outstanding issues.

  4. Space station static and dynamic analyses using parallel methods

    NASA Technical Reports Server (NTRS)

    Gupta, V.; Newell, J.; Storaasli, O.; Baddourah, M.; Bostic, S.

    1993-01-01

    Algorithms for high-performance parallel computers are applied to perform static analyses of large-scale Space Station finite-element models (FEMs). Several parallel-vector algorithms under development at NASA Langley are assessed. Sparse matrix solvers were found to be more efficient than banded symmetric or iterative solvers for the static analysis of large-scale applications. In addition, new sparse and 'out-of-core' solvers were found superior to substructure (superelement) techniques which require significant additional cost and time to perform static condensation during global FEM matrix generation as well as the subsequent recovery and expansion. A method to extend the fast parallel static solution techniques to reduce the computation time for dynamic analysis is also described. The resulting static and dynamic algorithms offer design economy for preliminary multidisciplinary design optimization and FEM validation against test modes. The algorithms are being optimized for parallel computers to solve one-million degrees-of-freedom (DOF) FEMs. The high-performance computers at NASA afforded effective software development, testing, efficient and accurate solution with timely system response and graphical interpretation of results rarely found in industry. Based on the author's experience, similar cooperation between industry and government should be encouraged for similar large-scale projects in the future.

  5. Strength and dynamic characteristics analyses of wound composite axial impeller

    NASA Astrophysics Data System (ADS)

    Wang, Jifeng; Olortegui-Yume, Jorge; Müller, Norbert

    2012-03-01

    A low cost, light weight, high performance composite material turbomachinery impeller with a uniquely designed blade patterns is analyzed. Such impellers can economically enable refrigeration plants to use water as a refrigerant (R718). A strength and dynamic characteristics analyses procedure is developed to assess the maximum stresses and natural frequencies of these wound composite axial impellers under operating loading conditions. Numerical simulation using FEM for two-dimensional and three-dimensional impellers was investigated. A commercially available software ANSYS is used for the finite element calculations. Analysis is done for different blade geometries and then suggestions are made for optimum design parameters. In order to avoid operating at resonance, which can make impellers suffer a significant reduction in the design life, the designer must calculate the natural frequency and modal shape of the impeller to analyze the dynamic characteristics. The results show that using composite Kevlar fiber/epoxy matrix enables the impeller to run at high tip speed and withstand the stresses, no critical speed will be matched during start-up and shut-down, and that mass imbalances of the impeller shall not pose a critical problem.

  6. [Dynamic Pulse Signal Processing and Analyzing in Mobile System].

    PubMed

    Chou, Yongxin; Zhang, Aihua; Ou, Jiqing; Qi, Yusheng

    2015-09-01

    In order to derive dynamic pulse rate variability (DPRV) signal from dynamic pulse signal in real time, a method for extracting DPRV signal was proposed and a portable mobile monitoring system was designed. The system consists of a front end for collecting and wireless sending pulse signal and a mobile terminal. The proposed method is employed to extract DPRV from dynamic pulse signal in mobile terminal, and the DPRV signal is analyzed both in the time domain and the frequency domain and also with non-linear method in real time. The results show that the proposed method can accurately derive DPRV signal in real time, the system can be used for processing and analyzing DPRV signal in real time.

  7. Dynamical Analyses for Developmental Science: A Primer for Intrigued Scientists

    ERIC Educational Resources Information Center

    DiDonato, M. D.; England, D.; Martin, C. L.; Amazeen, P. G.

    2013-01-01

    Dynamical systems theory is becoming more popular in social and developmental science. However, unfamiliarity with dynamical analysis techniques remains an obstacle for developmentalists who would like to quantitatively apply dynamics in their own research. The goal of this article is to address this issue by clearly and simply presenting several…

  8. Methods of dynamic spectral analysis by self-exciting autoregressive moving average models and their application to analysing biosignals.

    PubMed

    Schack, B; Bareshova, E; Grieszbach, G; Witte, H

    1995-05-01

    Dynamic methods in the spectral domain are necessary to analyse biological signals because of the frequently nonstationary character of the signals. The paper presents an adaptive procedure of fitting time-dependent ARMA models to nonstationary signals, which is suitable for on-line calculations. The properties of the model parameter estimations are examined, and in the stationary case are compared with the results of convergent estimation methods. On this basis time-varying spectral parameters with high temporal and spectral resolution are calculated, and the possibility of their application is shown in EEG analysis and laser-Doppler-flowmetry.

  9. Bias Analyses of Preclinical and Clinical D2 Dopamine Ligands: Studies with Immediate and Complex Signaling Pathways

    PubMed Central

    Brust, Tarsis F.; Hayes, Michael P.; Roman, David L.; Burris, Kevin D.

    2015-01-01

    G protein–coupled receptors (GPCRs) often activate multiple signaling pathways, and ligands may evoke functional responses through individual pathways. These unique responses provide opportunities for biased or functionally selective ligands to preferentially modulate one signaling pathway over another. Studies with several GPCRs have suggested that selective activation of signaling pathways downstream of a GPCR may lead to safer and more effective drug therapies. The dopamine D2 receptor (D2R) is one of the main drug targets in the therapies for Parkinson’s disease and schizophrenia. Recent studies suggest that selective modulation of individual signaling pathways downstream of the D2R may lead to safer antipsychotic drugs. In the present study, immediate effectors of the D2R (i.e., Gαi/o, Gβγ, β-arrestin recruitment) and more complex signaling pathways (i.e., extracellular signal-regulated kinase phosphorylation, heterologous sensitization, and dynamic mass redistribution) were examined in response to a series of D2R ligands. This was accomplished using Chinese hamster ovary cells stably expressing the human D2L dopamine receptor in the PathHunter β-Arrestin GPCR Assay Platform. The use of a uniform cellular background was designed to eliminate potential confounds associated with cell-to-cell variability, including expression levels of receptor as well as other components of signal transduction, including G protein subunits. Several well characterized and clinically relevant D2R ligands were evaluated across each signaling pathway in this cellular model. The most commonly used methods to measure ligand bias were compared. Functional selectivity analyses were also used as tools to explore the relative contribution of immediate D2R effectors for the activation of more complex signaling pathways. PMID:25539635

  10. Chaotic Ising-like dynamics in traffic signals

    PubMed Central

    Suzuki, Hideyuki; Imura, Jun-ichi; Aihara, Kazuyuki

    2013-01-01

    The green and red lights of a traffic signal can be viewed as the up and down states of an Ising spin. Moreover, traffic signals in a city interact with each other, if they are controlled in a decentralised way. In this paper, a simple model of such interacting signals on a finite-size two-dimensional lattice is shown to have Ising-like dynamics that undergoes a ferromagnetic phase transition. Probabilistic behaviour of the model is realised by chaotic billiard dynamics that arises from coupled non-chaotic elements. This purely deterministic model is expected to serve as a starting point for considering statistical mechanics of traffic signals. PMID:23350034

  11. Marginal Utility of Conditional Sensitivity Analyses for Dynamic Models

    EPA Science Inventory

    Background/Question/MethodsDynamic ecological processes may be influenced by many factors. Simulation models thatmimic these processes often have complex implementations with many parameters. Sensitivityanalyses are subsequently used to identify critical parameters whose uncertai...

  12. Summary of dynamic analyses of selected NSS buildings. Final report

    SciTech Connect

    Beck, J.E.

    1980-07-01

    This report covers the collapse analyses of floor-over-basement areas. The floors were separated into floor systems and were analyzed 'as built' and for various upgrading configurations through an examination of individual elements. The purpose of the report is two-fold: first, to increase the data base of analyzed 'as built' NSS building floors; and second, to determine the expedient upgrading potentials of NSS building floors. This report summarizes the results of the collapse analyses of the 11 NSS buildings examined in this study. The results of the 'as built' analyses are then grouped with the collapse analyses of 36 NSS buildings to provide a population of 46 buildings (one building was reexamined). The predicted collapse overpressures, examined previously by Wiehle (1974), of the weakest floor element by building and by floor system are presented in the form of histograms and cumulative frequency distributions. The effect of frame type on the collapse strength of the floor elements was examined as in the previous report (Wiehle, 1974). This report also summarizes, for the 11 buildings analyzed herein, the upgrading potentials of floor elements grouped by individual element, floor system and building. Preliminary indications of these collapse analyses indicate that the best way to assess which building and/or element is most upgradable is to look for elements, especially slabs or pan-joist systems, having the greatest span.

  13. Dynamics of a sensory signaling network in a unicellular eukaryote.

    PubMed

    Foster, Kenneth W; Josef, Keith; Saranak, Jureepan; Tuck, Ned

    2006-01-01

    The processing components and the dynamic signaling network that an individual cell uses to do signal integration and make decisions based on multiple sensory inputs are being identified in a well studied free-swimming unicellular green algal model organism, Chlamydomonas. It has many sensory photoreceptors and measurable behavior associated with its orienting and swimming with respect to light sources in its environment. Study of the dynamics of the beating of its two steering cilia reveals their complex specialization.

  14. Dynamic analyses of viscoelastic dielectric elastomers incorporating viscous damping effect

    NASA Astrophysics Data System (ADS)

    Zhang, Junshi; Zhao, Jianwen; Chen, Hualing; Li, Dichen

    2017-01-01

    In this paper, based on the standard linear solid rheological model, a dynamics model of viscoelastic dielectric elastomers (DEs) is developed with incorporation of viscous damping effect. Numerical calculations are employed to predict the damping effect on the dynamic performance of DEs. With increase of damping force, the DEs show weak nonlinearity and vibration strength. Phase diagrams and Poincaré maps are utilized to detect the dynamic stability of DEs, and the results indicate that a transition from aperiodic vibration to quasi-periodic vibration occurs with enlargement of damping force. The resonance properties of DEs including damping effect are subsequently analyzed, demonstrating a reduction of resonant frequency and resonance peak with increase of damping force.

  15. Dynamic Programming Algorithms and Analyses for Nonserial Networks. Part I.

    DTIC Science & Technology

    1983-01-01

    Journal of Mathematical Analysis and Applications , Vol...Multistage Systems," Journal of Mathematical Analysis and Applications , Vol. 21, 1968, pp. 426-430. 4. Bellman, R.E.,A.O. Esogbue, and I. Nabeshima...the Secondary Optimization Problem in Nonserial Dynamic Programming," Journal of Mathematical Analysis and Applications , Vol. 27, 1969, pp. 565-574.

  16. The dynamic mechanism of noisy signal decoding in gene regulation

    PubMed Central

    Liu, Peijiang; Wang, Haohua; Huang, Lifang; Zhou, Tianshou

    2017-01-01

    Experimental evidence supports that signaling pathways can induce different dynamics of transcription factor (TF) activation, but how an input signal is encoded by such a dynamic, noisy TF and further decoded by downstream genes remains largely unclear. Here, using a system of stochastic transcription with signal regulation, we show that (1) keeping the intensity of the signal noise invariant but prolonging the signal duration can both enhance the mutual information (MI) and reduce the energetic cost (EC); (2) if the signal duration is fixed, the larger MI needs the larger EC, but if the signal period is fixed, there is an optimal time that the signal spends at one lower branch, such that MI reaches the maximum; (3) if both the period and the duration are simultaneously fixed, increasing the input noise can always enhance MI in the case of transcription regulation rather than in the case of degradation regulation. In addition, we find that the input noise can induce stochastic focusing in a regulation-dependent manner. These results reveal not only the dynamic mechanism of noisy signal decoding in gene regulation but also the essential role of external noise in controlling gene expression levels. PMID:28176840

  17. Geophysical and fluid dynamical analyses in physical volcanology

    NASA Astrophysics Data System (ADS)

    Rogers, Patricia Grizzaffi

    Volcanism is a predominant process on the terrestrial planets, and studies of physical volcanologic processes provide fundamental insight into the evolution of a planet's surface and interior. This work combines theoretical modeling, field observations, and studies of planetary surfaces in an integrated approach to understanding the mechanical and dynamic processes associated with volcanism. By understanding the basic dynamics associated with terrestrial volcanic processes, we hope to better understand the evolution of other planetary surfaces for which only remote sensing data are available. The focus of this work is the physics of volcanism in space and time, with an emphasis on regions that are dominated by volcanism such as the Hawaiian islands, and on studies of lava flow emplacement. Applying our knowledge of volcanic processes on Earth to studies of Venusian geology and geophysics is also important for this investigation because volcanism has been a primary process in creating and modifying landforms on that planet. This analysis of geophysical and fluid dynamic processes associated with physical volcanology first focuses on the relationship between volcanic and tectonic processes and the associated stress environments. Specifically, through analytical modeling we investigate the regional stresses associated with Bell Regio, a volcanic highland on Venus, and structural features believed to be a consequence of lithospheric flexure due to volcanic loading. The relationship between the tectonic features surrounding a volcanic edifice and stresses associated with magma chamber inflation are also examined through finite element analysis. The implications of a change in volcanic style and lithospheric thickness over time are discussed. Next, factors that affect the dynamics of lava flow emplacement are examined through a combination ot theoretical modeling and field measurements. Downflow changes in rheology and lava channel formation under conditions of varying

  18. Genetic and Dynamic Analyses of Murine Peak Bone Density

    DTIC Science & Technology

    1999-10-01

    4 vBMD loci shared with femurs (1, 4, 14, & 18) and 2 unique loci (Chr 7 & 9). Lastly, a new DEXA instrument for mice, the PIXhnus, has been...late 1999. The summarized results for the femoral total BMD analyses were: a) Genome wide scans for co-segregation of genetic marker data with high or...possible tools for drug discovery aimed at exogenous manipulation of bone density. New Instrumentation - PIXImus DEXA . We have been testing a dual energy

  19. Dynamical collective calculation of supernova neutrino signals.

    PubMed

    Gava, Jérôme; Kneller, James; Volpe, Cristina; McLaughlin, G C

    2009-08-14

    We present the first calculations with three flavors of collective and shock wave effects for neutrino propagation in core-collapse supernovae using hydrodynamical density profiles and the S matrix formalism. We explore the interplay between the neutrino-neutrino interaction and the effects of multiple resonances upon the time signal of positrons in supernova observatories. A specific signature is found for the inverted hierarchy and a large third neutrino mixing angle and we predict, in this case, a dearth of lower energy positrons in Cherenkov detectors midway through the neutrino signal and the simultaneous revelation of valuable information about the original fluxes. We show that this feature is also observable with current generation neutrino detectors at the level of several sigmas.

  20. Dynamic force signal processing system of a robot manipulator

    NASA Technical Reports Server (NTRS)

    Uchiyama, M.; Kitagaki, K.; Hakomori, K.

    1987-01-01

    If dynamic noises such as those caused by the inertia forces of the hand can be eliminated from the signal of the force sensor installed on the wrist of the robot manipulator and if the necessary information of the external force can be detected with high sensitivity and high accuracy, a fine force feedback control for robots used in high speed and various fields will be possible. As the dynamic force sensing system, an external force estimate method with the extended Kalman filter is suggested and simulations and tests for a one axis force were performed. Later a dynamic signal processing system of six axes was composed and tested. The results are presented.

  1. Progressive alignment of genomic signals by multiple dynamic time warping.

    PubMed

    Skutkova, Helena; Vitek, Martin; Sedlar, Karel; Provaznik, Ivo

    2015-11-21

    This paper presents the utilization of progressive alignment principle for positional adjustment of a set of genomic signals with different lengths. The new method of multiple alignment of signals based on dynamic time warping is tested for the purpose of evaluating the similarity of different length genes in phylogenetic studies. Two sets of phylogenetic markers were used to demonstrate the effectiveness of the evaluation of intraspecies and interspecies genetic variability. The part of the proposed method is modification of pairwise alignment of two signals by dynamic time warping with using correlation in a sliding window. The correlation based dynamic time warping allows more accurate alignment dependent on local homologies in sequences without the need of scoring matrix or evolutionary models, because mutual similarities of residues are included in the numerical code of signals.

  2. Coupled Thermo-Mechanical Analyses of Dynamically Loaded Rubber Cylinders

    NASA Technical Reports Server (NTRS)

    Johnson, Arthur R.; Chen, Tzi-Kang

    2000-01-01

    A procedure that models coupled thermo-mechanical deformations of viscoelastic rubber cylinders by employing the ABAQUS finite element code is described. Computational simulations of hysteretic heating are presented for several tall and short rubber cylinders both with and without a steel disk at their centers. The cylinders are compressed axially and are then cyclically loaded about the compressed state. The non-uniform hysteretic heating of the rubber cylinders containing a steel disk is presented. The analyses performed suggest that the coupling procedure should be considered for further development as a design tool for rubber degradation studies.

  3. Improved Aerodynamic Influence Coefficients for Dynamic Aeroelastic Analyses

    NASA Astrophysics Data System (ADS)

    Gratton, Patrice

    2011-12-01

    Currently at Bombardier Aerospace, aeroelastic analyses are performed using the Doublet Lattice Method (DLM) incorporated in the NASTRAN solver. This method proves to be very reliable and fast in preliminary design stages where wind tunnel experimental results are often not available. Unfortunately, the geometric simplifications and limitations of the DLM, based on the lifting surfaces theory, reduce the ability of this method to give reliable results for all flow conditions, particularly in transonic flow. Therefore, a new method has been developed involving aerodynamic data from high-fidelity CFD codes which solve the Euler or Navier-Stokes equations. These new aerodynamic loads are transmitted to the NASTRAN aeroelastic module through improved aerodynamic influence coefficients (AIC). A cantilevered wing model is created from the Global Express structural model and a set of natural modes is calculated for a baseline configuration of the structure. The baseline mode shapes are then combined with an interpolation scheme to deform the 3-D CFD mesh necessary for Euler and Navier-Stokes analyses. An uncoupled approach is preferred to allow aerodynamic information from different CFD codes. Following the steady state CFD analyses, pressure differences ( DeltaCp), calculated between the deformed models and the original geometry, lead to aerodynamic loads which are transferred to the DLM model. A modal-based AIC method is applied to the aerodynamic matrices of NASTRAN based on a least-square approximation to evaluate aerodynamic loads of a different wing configuration which displays similar types of mode shapes. The methodology developed in this research creates weighting factors based on steady CFD analyses which have an equivalent reduced frequency of zero. These factors are applied to both the real and imaginary part of the aerodynamic matrices as well as all reduced frequencies used in the PK-Method which solves flutter problems. The modal-based AIC method

  4. Dynamics of Mechanical Signal Transmission through Prestressed Stress Fibers

    PubMed Central

    Hwang, Yongyun; Barakat, Abdul I.

    2012-01-01

    Transmission of mechanical stimuli through the actin cytoskeleton has been proposed as a mechanism for rapid long-distance mechanotransduction in cells; however, a quantitative understanding of the dynamics of this transmission and the physical factors governing it remains lacking. Two key features of the actin cytoskeleton are its viscoelastic nature and the presence of prestress due to actomyosin motor activity. We develop a model of mechanical signal transmission through prestressed viscoelastic actin stress fibers that directly connect the cell surface to the nucleus. The analysis considers both temporally stationary and oscillatory mechanical signals and accounts for cytosolic drag on the stress fibers. To elucidate the physical parameters that govern mechanical signal transmission, we initially focus on the highly simplified case of a single stress fiber. The results demonstrate that the dynamics of mechanical signal transmission depend on whether the applied force leads to transverse or axial motion of the stress fiber. For transverse motion, mechanical signal transmission is dominated by prestress while fiber elasticity has a negligible effect. Conversely, signal transmission for axial motion is mediated uniquely by elasticity due to the absence of a prestress restoring force. Mechanical signal transmission is significantly delayed by stress fiber material viscosity, while cytosolic damping becomes important only for longer stress fibers. Only transverse motion yields the rapid and long-distance mechanical signal transmission dynamics observed experimentally. For simple networks of stress fibers, mechanical signals are transmitted rapidly to the nucleus when the fibers are oriented largely orthogonal to the applied force, whereas the presence of fibers parallel to the applied force slows down mechanical signal transmission significantly. The present results suggest that cytoskeletal prestress mediates rapid mechanical signal transmission and allows

  5. Dynamics of mechanical signal transmission through prestressed stress fibers.

    PubMed

    Hwang, Yongyun; Barakat, Abdul I

    2012-01-01

    Transmission of mechanical stimuli through the actin cytoskeleton has been proposed as a mechanism for rapid long-distance mechanotransduction in cells; however, a quantitative understanding of the dynamics of this transmission and the physical factors governing it remains lacking. Two key features of the actin cytoskeleton are its viscoelastic nature and the presence of prestress due to actomyosin motor activity. We develop a model of mechanical signal transmission through prestressed viscoelastic actin stress fibers that directly connect the cell surface to the nucleus. The analysis considers both temporally stationary and oscillatory mechanical signals and accounts for cytosolic drag on the stress fibers. To elucidate the physical parameters that govern mechanical signal transmission, we initially focus on the highly simplified case of a single stress fiber. The results demonstrate that the dynamics of mechanical signal transmission depend on whether the applied force leads to transverse or axial motion of the stress fiber. For transverse motion, mechanical signal transmission is dominated by prestress while fiber elasticity has a negligible effect. Conversely, signal transmission for axial motion is mediated uniquely by elasticity due to the absence of a prestress restoring force. Mechanical signal transmission is significantly delayed by stress fiber material viscosity, while cytosolic damping becomes important only for longer stress fibers. Only transverse motion yields the rapid and long-distance mechanical signal transmission dynamics observed experimentally. For simple networks of stress fibers, mechanical signals are transmitted rapidly to the nucleus when the fibers are oriented largely orthogonal to the applied force, whereas the presence of fibers parallel to the applied force slows down mechanical signal transmission significantly. The present results suggest that cytoskeletal prestress mediates rapid mechanical signal transmission and allows

  6. Dynamic Vibrotactile Signals for Forward Collision Avoidance Warning Systems

    PubMed Central

    Meng, Fanxing; Gray, Rob; Ho, Cristy; Ahtamad, Mujthaba

    2015-01-01

    Objective: Four experiments were conducted in order to assess the effectiveness of dynamic vibrotactile collision-warning signals in potentially enhancing safe driving. Background: Auditory neuroscience research has demonstrated that auditory signals that move toward a person are more salient than those that move away. If this looming effect were found to extend to the tactile modality, then it could be utilized in the context of in-car warning signal design. Method: The effectiveness of various vibrotactile warning signals was assessed using a simulated car-following task. The vibrotactile warning signals consisted of dynamic toward-/away-from-torso cues (Experiment 1), dynamic versus static vibrotactile cues (Experiment 2), looming-intensity- and constant-intensity-toward-torso cues (Experiment 3), and static cues presented on the hands or on the waist, having either a low or high vibration intensity (Experiment 4). Results: Braking reaction times (BRTs) were significantly faster for toward-torso as compared to away-from-torso cues (Experiments 1 and 2) and static cues (Experiment 2). This difference could not have been attributed to differential responses to signals delivered to different body parts (i.e., the waist vs. hands; Experiment 4). Embedding a looming-intensity signal into the toward-torso signal did not result in any additional BRT benefits (Experiment 3). Conclusion: Dynamic vibrotactile cues that feel as though they are approaching the torso can be used to communicate information concerning external events, resulting in a significantly faster reaction time to potential collisions. Application: Dynamic vibrotactile warning signals that move toward the body offer great potential for the design of future in-car collision-warning system. PMID:25850161

  7. Unsteady flow and dynamic response analyses for helicopter rotor blades

    NASA Technical Reports Server (NTRS)

    Bratanow, T.

    1979-01-01

    Research is presented on helicopter rotor blade vibration and on two and three dimensional analyses of unsteady incompressible viscous flow past oscillating helicopter rotor blades. A summary is presented of the two international research collaborations which resulted from the NASA project: the collaboration under the auspices of NATO between the University of Wisconsin-Milwaukee, University of Brussels, Belgium and the Aerodynamics Research Establishment in Goettingen, West Germany, and the collaboration under the auspices of the National Science Foundation between UWM and the University of Hamburg and the Ship Research Establishment in Hamburg, West Germany. A summary is given of the benefits from the NASA project to UWM, the College of Engineering and Applied Science, and the participants on the project.

  8. Thermo-Mechanical Analyses of Dynamically Loaded Rubber Cylinders

    NASA Technical Reports Server (NTRS)

    Johnson, Arthur R.; Chen, Tzi-Kang

    2002-01-01

    Thick rubber components are employed by the Army to carry large loads. In tanks, rubber covers road wheels and track systems to protect roadways. It is difficult for design engineers to simulate the details of the hysteretic heating for large strain viscoelastic deformations. In this study, an approximation to the viscoelastic energy dissipated per unit time is investigated for use in estimating mechanically induced viscoelastic heating. Coupled thermo-mechanical simulations of large cyclic deformations of rubber cylinders are presented. The cylinders are first compressed axially and then cyclically loaded about the compressed state. Details of the algorithm and some computational issues are discussed. The coupled analyses are conducted for tall and short rubber cylinders both with and without imbedded metal disks.

  9. Dynamic and thermal analyses of flexible structures in orbit

    NASA Astrophysics Data System (ADS)

    Lin, Chijie

    Due to the launch cost and functional requirements, space structures, such as satellite antenna, deployable structures, solar sails, the space station, and solar panels, are necessarily built lightweight, large, and very flexible. These space structures undergo large orbital rigid body motions as well as large structural deformations caused by gravitational force and other disturbances, such as shuttle jet impingement loading, deployment factor, thermal effects, and debris impact. It is of utmost importance to study thoroughly the dynamic behavior of flexible structures in orbit under various external forces. In this study, first a finite element methodology program based on the absolute nodal coordinate formulation is developed to determine the coupled structural and orbital response of the flexible structure under gravitational and external loading, i.e., gravitational force, impact force, and jet impingement, and thermal loading. It is found from the simulation results that pitch and structural response of the flexible structures are greatly impacted by the initial and loading conditions, such as orbit eccentricity, initial misalignment, etc. The absolute nodal coordinate formulation may lead to inaccurate results due to the fact that the orbit radius is used for element coordinate, which is much greater than the amplitude of the pitch (attitude) motion and deformations of the orbiting structures. Therefore, to improve the accuracy of structural response in the simulation, a floating (moving) frame that is attached with the orbiting structure's center of mass and that moves parallel to the inertia frame fixed at the Earth's center is introduced to separate the attitude motion and structural deformation from the orbit radius. The finite element formulation is developed in this parallel reference frame system for two and three dimensional beam structures. It is then used to study dynamic response of flexible structures in two and three dimensional orbits. In some

  10. Information dynamics in cardiorespiratory analyses: application to controlled breathing.

    PubMed

    Widjaja, Devy; Faes, Luca; Montalto, Alessandro; Van Diest, Ilse; Marinazzo, Daniele; Van Huffel, Sabine

    2014-01-01

    Voluntary adjustment of the breathing pattern is widely used to deal with stress-related conditions. In this study, effects of slow and fast breathing with a low and high inspiratory to expiratory time on heart rate variability (HRV) are evaluated by means of information dynamics. Information transfer is quantified both as the traditional transfer entropy as well as the cross entropy, where the latter does not condition on the past of HRV, thereby taking the highly unidirectional relation between respiration and heart rate into account. The results show that the cross entropy is more suited to quantify cardiorespiratory information transfer as this measure increases during slow breathing, indicating the increased cardiorespiratory coupling and suggesting the shift towards vagal activation during slow breathing. Additionally we found that controlled breathing, either slow or fast, results as well in an increase in cardiorespiratory coupling, compared to spontaneous breathing, which demonstrates the beneficial effects of instructed breathing.

  11. Dynamical states, possibilities and propagation of stress signal

    PubMed Central

    Malik, Md. Zubbair; Ali, Shahnawaz; Singh, Soibam Shyamchand; Ishrat, Romana; Singh, R. K. Brojen

    2017-01-01

    The stress driven dynamics of Notch-Wnt-p53 cross-talk is subjected to a few possible dynamical states governed by simple fractal rules, and allowed to decide its own fate by choosing one of these states which are contributed from long range correlation with varied fluctuations due to active molecular interaction. The topological properties of the networks corresponding to these dynamical states have hierarchical features with assortive structure. The stress signal driven by nutlin and modulated by mediator GSK3 acts as anti-apoptotic signal in this system, whereas, the stress signal driven by Axin and modulated by GSK3 behaves as anti-apoptotic for a certain range of Axin and GSK3 interaction, and beyond which the signal acts as favor-apoptotic signal. However, this stress system prefers to stay in an active dynamical state whose counterpart complex network is closest to hierarchical topology with exhibited roles of few interacting hubs. During the propagation of stress signal, the system allows the propagator pathway to inherit all possible properties of the state to the receiver pathway/pathways with slight modifications, indicating efficient information processing and democratic sharing of responsibilities in the system via cross-talk. The increase in the number of cross-talk pathways in the system favors to establish self-organization. PMID:28106087

  12. Analysing the temporal dynamics of model performance for hydrological models

    NASA Astrophysics Data System (ADS)

    Reusser, D. E.; Blume, T.; Schaefli, B.; Zehe, E.

    2009-07-01

    The temporal dynamics of hydrological model performance gives insights into errors that cannot be obtained from global performance measures assigning a single number to the fit of a simulated time series to an observed reference series. These errors can include errors in data, model parameters, or model structure. Dealing with a set of performance measures evaluated at a high temporal resolution implies analyzing and interpreting a high dimensional data set. This paper presents a method for such a hydrological model performance assessment with a high temporal resolution and illustrates its application for two very different rainfall-runoff modeling case studies. The first is the Wilde Weisseritz case study, a headwater catchment in the eastern Ore Mountains, simulated with the conceptual model WaSiM-ETH. The second is the Malalcahuello case study, a headwater catchment in the Chilean Andes, simulated with the physics-based model Catflow. The proposed time-resolved performance assessment starts with the computation of a large set of classically used performance measures for a moving window. The key of the developed approach is a data-reduction method based on self-organizing maps (SOMs) and cluster analysis to classify the high-dimensional performance matrix. Synthetic peak errors are used to interpret the resulting error classes. The final outcome of the proposed method is a time series of the occurrence of dominant error types. For the two case studies analyzed here, 6 such error types have been identified. They show clear temporal patterns, which can lead to the identification of model structural errors.

  13. Analysing the temporal dynamics of model performance for hydrological models

    NASA Astrophysics Data System (ADS)

    Reusser, D. E.; Blume, T.; Schaefli, B.; Zehe, E.

    2008-11-01

    The temporal dynamics of hydrological model performance gives insights into errors that cannot be obtained from global performance measures assigning a single number to the fit of a simulated time series to an observed reference series. These errors can include errors in data, model parameters, or model structure. Dealing with a set of performance measures evaluated at a high temporal resolution implies analyzing and interpreting a high dimensional data set. This paper presents a method for such a hydrological model performance assessment with a high temporal resolution and illustrates its application for two very different rainfall-runoff modeling case studies. The first is the Wilde Weisseritz case study, a headwater catchment in the eastern Ore Mountains, simulated with the conceptual model WaSiM-ETH. The second is the Malalcahuello case study, a headwater catchment in the Chilean Andes, simulated with the physics-based model Catflow. The proposed time-resolved performance assessment starts with the computation of a large set of classically used performance measures for a moving window. The key of the developed approach is a data-reduction method based on self-organizing maps (SOMs) and cluster analysis to classify the high-dimensional performance matrix. Synthetic peak errors are used to interpret the resulting error classes. The final outcome of the proposed method is a time series of the occurrence of dominant error types. For the two case studies analyzed here, 6 such error types have been identified. They show clear temporal patterns which can lead to the identification of model structural errors.

  14. Regulation of Mitoflash Biogenesis and Signaling by Mitochondrial Dynamics

    PubMed Central

    Li, Wenwen; Sun, Tao; Liu, Beibei; Wu, Di; Qi, Wenfeng; Wang, Xianhua; Ma, Qi; Cheng, Heping

    2016-01-01

    Mitochondria are highly dynamic organelles undergoing constant network reorganization and exhibiting stochastic signaling events in the form of mitochondrial flashes (mitoflashes). Here we investigate whether and how mitochondrial network dynamics regulate mitoflash biogenesis and signaling. We found that mitoflash frequency was largely invariant when network fragmentized or redistributed in the absence of mitofusin (Mfn) 1, Mfn2, or Kif5b. However, Opa1 deficiency decreased spontaneous mitoflash frequency due to superimposing changes in respiratory function, whereas mitoflash response to non-metabolic stimulation was unchanged despite network fragmentation. In Drp1- or Mff-deficient cells whose mitochondria hyperfused into a single whole-cell reticulum, the frequency of mitoflashes of regular amplitude and duration was again unaltered, although brief and low-amplitude “miniflashes” emerged because of improved detection ability. As the network reorganized, however, the signal mass of mitoflash signaling was dynamically regulated in accordance with the degree of network connectivity. These findings demonstrate a novel functional role of mitochondrial network dynamics and uncover a magnitude- rather than frequency-modulatory mechanism in the regulation of mitoflash signaling. In addition, our data support a stochastic trigger model for the ignition of mitoflashes. PMID:27623243

  15. Quantitative dynamic imaging of immune cell signalling using lentiviral gene transfer.

    PubMed

    Bagnall, J; Boddington, C; Boyd, J; Brignall, R; Rowe, W; Jones, N A; Schmidt, L; Spiller, D G; White, M R H; Paszek, P

    2015-06-01

    Live-cell imaging of fluorescent fusion proteins has transformed our understanding of mammalian cell signalling and function. However, some cellular systems such as immune cells are unsuitable or refractory to many existing transgene delivery methods thus limiting systematic analyses. Here, a flexible lentiviral gene transfer platform for dynamic time-lapse imaging has been developed and validated with single-molecule spectroscopy, mathematical modelling and transcriptomics and used for analysis of a set of inflammation-related signalling networks. Time-lapse imaging of nuclear factor kappa B (NF-κB), signal transducer and activator of transcription (STATs) and nuclear factor of activated T-cells (NFAT) in mammalian immune cell lines provided evidence for heterogeneous temporal encoding of inflammatory signals. In particular, the absolute quantification of single-cell responses over time via fluorescent correlation spectroscopy (FCS) showed that NF-κB p65 activation in response to tumour necrosis factor α (TNFα) was differentially encoded in variable amplitude of nuclear translocation between immune and non-immune cells. The absolute number of activated molecules was dictated in part by the cell size, suggesting a morphology-dependent regulatory mechanism. The developed platform will enable further absolute quantitative analyses of the dynamic interactions between signalling networks, in and between individual cells, allowing better integration with mathematical models of signalling networks.

  16. Single-Molecule Protein Conformational Dynamics in Cell Signaling

    SciTech Connect

    Lu, H PETER.

    2004-08-22

    We have demonstrated the application of single-molecule imaging and ultrafast spectroscopy to probe protein conformational dynamics in solution and in lipid bilayers. Dynamic protein-protein interactions involve significant conformational motions that initiate chain reactions leading to specific cellular responses. We have carried out a single molecule study of dynamic protein-protein interactions in a GTPase intracellular signaling protein Cdc42 in complex with a downstream effector protein, WASP. We were able to probe hydrophobic interactions significant to Cdc42/WASP recognition. Single molecule fluorescence intensity and polarization measurements have revealed the dynamic and inhomogeneous nature of protein-protein interactions within the Cdc42/WASP complex that is characterized by structured distributions of conformational fluctuation rates. Conducting a single-molecule fluorescence anisotropy study of calmodulin (CaM), a regulatory protein for calcium-dependent cell signaling, we were able to probe CaM conformational dynamics at a wide time scale. In this study, CaM contains a site-specifically inserted tetra-cysteine motif that reacted with FlAsH, a biarsenic fluorescein derivative that can be rotationally locked to the host protein. The study provided direct characterization of the nanosecond motions of CaM tethered to a biologically compatible surface under physiological buffer solution. The unique technical approaches are applicable of studying single-molecule dynamics of protein conformational motions and protein-protein interactions at a wide time range without the signal convolution of probe-dye molecule motions

  17. A fluorescent hormone biosensor reveals the dynamics of jasmonate signalling in plants.

    PubMed

    Larrieu, Antoine; Champion, Antony; Legrand, Jonathan; Lavenus, Julien; Mast, David; Brunoud, Géraldine; Oh, Jaesung; Guyomarc'h, Soazig; Pizot, Maxime; Farmer, Edward E; Turnbull, Colin; Vernoux, Teva; Bennett, Malcolm J; Laplaze, Laurent

    2015-01-16

    Activated forms of jasmonic acid (JA) are central signals coordinating plant responses to stresses, yet tools to analyse their spatial and temporal distribution are lacking. Here we describe a JA perception biosensor termed Jas9-VENUS that allows the quantification of dynamic changes in JA distribution in response to stress with high spatiotemporal sensitivity. We show that Jas9-VENUS abundance is dependent on bioactive JA isoforms, the COI1 co-receptor, a functional Jas motif and proteasome activity. We demonstrate the utility of Jas9-VENUS to analyse responses to JA in planta at a cellular scale, both quantitatively and dynamically. This included using Jas9-VENUS to determine the cotyledon-to-root JA signal velocities on wounding, revealing two distinct phases of JA activity in the root. Our results demonstrate the value of developing quantitative sensors such as Jas9-VENUS to provide high-resolution spatiotemporal data about hormone distribution in response to plant abiotic and biotic stresses.

  18. Dynamic Ca2+ signal modalities in the vascular endothelium

    PubMed Central

    Taylor, Mark S.; Francis, Michael; Qian, Xun; Solodushko, Viktoriya

    2012-01-01

    The endothelium is vital to normal vasoregulation. Although acute vasodilation associated with broad endothelial Ca2+ elevation is well-known, the control and targeting of Ca2+ dependent signals in the endothelium is poorly understood. Recent studies have revealed localized IP3-motivated Ca2+ events occurring basally along the intima that may provide the fundamental basis for various endothelial influences. Here, we provide an overview of dynamic endothelial Ca2+ signals and discuss the potential role of these signals in constant endothelial control of arterial tone and the titration of functional responses in vivo. In particular, we focus on the functional architecture contributing to the properties and ultimate impact of these signals and explore new avenues in evaluating their prevalence and specific modalities in intact tissue. Finally, we discuss spatial and temporal effector recruitment through modification of these inherent signals. It is suggested that endothelial Ca2+ signaling is a continuum in which the specific framework of store-release components and cellular targets along the endothelium allows for differential modes of Ca2+ signal expansion and distinctive profiles of effector recruitment. The precise composition and distribution of these inherent components may underlie dynamic endothelial control and specialized functions of different vascular beds. PMID:22443172

  19. An Integrated Signaling-Encryption Mechanism to Reduce Error Propagation in Wireless Communications: Performance Analyses

    SciTech Connect

    Olama, Mohammed M; Matalgah, Mustafa M; Bobrek, Miljko

    2015-01-01

    Traditional encryption techniques require packet overhead, produce processing time delay, and suffer from severe quality of service deterioration due to fades and interference in wireless channels. These issues reduce the effective transmission data rate (throughput) considerably in wireless communications, where data rate with limited bandwidth is the main constraint. In this paper, performance evaluation analyses are conducted for an integrated signaling-encryption mechanism that is secure and enables improved throughput and probability of bit-error in wireless channels. This mechanism eliminates the drawbacks stated herein by encrypting only a small portion of an entire transmitted frame, while the rest is not subject to traditional encryption but goes through a signaling process (designed transformation) with the plaintext of the portion selected for encryption. We also propose to incorporate error correction coding solely on the small encrypted portion of the data to drastically improve the overall bit-error rate performance while not noticeably increasing the required bit-rate. We focus on validating the signaling-encryption mechanism utilizing Hamming and convolutional error correction coding by conducting an end-to-end system-level simulation-based study. The average probability of bit-error and throughput of the encryption mechanism are evaluated over standard Gaussian and Rayleigh fading-type channels and compared to the ones of the conventional advanced encryption standard (AES).

  20. Towards blueprints for network architecture, biophysical dynamics and signal transduction.

    PubMed

    Coombes, Stephen; Doiron, Brent; Josić, Kresimir; Shea-Brown, Eric

    2006-12-15

    We review mathematical aspects of biophysical dynamics, signal transduction and network architecture that have been used to uncover functionally significant relations between the dynamics of single neurons and the networks they compose. We focus on examples that combine insights from these three areas to expand our understanding of systems neuroscience. These range from single neuron coding to models of decision making and electrosensory discrimination by networks and populations and also coincidence detection in pairs of dendrites and dynamics of large networks of excitable dendritic spines. We conclude by describing some of the challenges that lie ahead as the applied mathematics community seeks to provide the tools which will ultimately underpin systems neuroscience.

  1. Nonlinear Dynamic Analysis of Scalp EEG Epileptic Signals

    NASA Astrophysics Data System (ADS)

    Blanco, Susana A.; Creso, Judith; Figliola, Alejandra; Quiroga, Rodrigo Quian; Rosso, Osvaldo A.

    Noisy signals obtained during a tonic-clonic epileptic seizure, are usually neglected for visual inspection by the physicians due to the presence of muscle artifacts. Although noise obscures completely the recording, information about the underlying brain activity can be obtained by filtering, through the Orthogonal Wavelet Transforms, those frequencies bands associated with muscle activity. After generating a "noise free" signal by removing the muscle artifacts with wavelets, a dynamical analysis of the brain behavior will be performed by using nonlinear dynamics methods. The values for nonlinear metric invariants, like the correlation dimension and the maximum Lyapunov exponent, confirm that the brain dynamical behavior is more ordered during the epileptic seizure than pre-seizure stage.

  2. Discrete dynamic modeling of T cell survival signaling networks

    NASA Astrophysics Data System (ADS)

    Zhang, Ranran

    2009-03-01

    Biochemistry-based frameworks are often not applicable for the modeling of heterogeneous regulatory systems that are sparsely documented in terms of quantitative information. As an alternative, qualitative models assuming a small set of discrete states are gaining acceptance. This talk will present a discrete dynamic model of the signaling network responsible for the survival and long-term competence of cytotoxic T cells in the blood cancer T-LGL leukemia. We integrated the signaling pathways involved in normal T cell activation and the known deregulations of survival signaling in leukemic T-LGL, and formulated the regulation of each network element as a Boolean (logic) rule. Our model suggests that the persistence of two signals is sufficient to reproduce all known deregulations in leukemic T-LGL. It also indicates the nodes whose inactivity is necessary and sufficient for the reversal of the T-LGL state. We have experimentally validated several model predictions, including: (i) Inhibiting PDGF signaling induces apoptosis in leukemic T-LGL. (ii) Sphingosine kinase 1 and NFκB are essential for the long-term survival of T cells in T-LGL leukemia. (iii) T box expressed in T cells (T-bet) is constitutively activated in the T-LGL state. The model has identified potential therapeutic targets for T-LGL leukemia and can be used for generating long-term competent CTL necessary for tumor and cancer vaccine development. The success of this model, and of other discrete dynamic models, suggests that the organization of signaling networks has an determining role in their dynamics. Reference: R. Zhang, M. V. Shah, J. Yang, S. B. Nyland, X. Liu, J. K. Yun, R. Albert, T. P. Loughran, Jr., Network Model of Survival Signaling in LGL Leukemia, PNAS 105, 16308-16313 (2008).

  3. GNSS Signal Tracking Performance Improvement for Highly Dynamic Receivers by Gyroscopic Mounting Crystal Oscillator.

    PubMed

    Abedi, Maryam; Jin, Tian; Sun, Kewen

    2015-08-31

    In this paper, the efficiency of the gyroscopic mounting method is studied for a highly dynamic GNSS receiver's reference oscillator for reducing signal loss. Analyses are performed separately in two phases, atmospheric and upper atmospheric flights. Results show that the proposed mounting reduces signal loss, especially in parts of the trajectory where its probability is the highest. This reduction effect appears especially for crystal oscillators with a low elevation angle g-sensitivity vector. The gyroscopic mounting influences frequency deviation or jitter caused by dynamic loads on replica carrier and affects the frequency locked loop (FLL) as the dominant tracking loop in highly dynamic GNSS receivers. In terms of steady-state load, the proposed mounting mostly reduces the frequency deviation below the one-sigma threshold of FLL (1σ(FLL)). The mounting method can also reduce the frequency jitter caused by sinusoidal vibrations and reduces the probability of signal loss in parts of the trajectory where the other error sources accompany this vibration load. In the case of random vibration, which is the main disturbance source of FLL, gyroscopic mounting is even able to suppress the disturbances greater than the three-sigma threshold of FLL (3σ(FLL)). In this way, signal tracking performance can be improved by the gyroscopic mounting method for highly dynamic GNSS receivers.

  4. GNSS Signal Tracking Performance Improvement for Highly Dynamic Receivers by Gyroscopic Mounting Crystal Oscillator

    PubMed Central

    Abedi, Maryam; Jin, Tian; Sun, Kewen

    2015-01-01

    In this paper, the efficiency of the gyroscopic mounting method is studied for a highly dynamic GNSS receiver’s reference oscillator for reducing signal loss. Analyses are performed separately in two phases, atmospheric and upper atmospheric flights. Results show that the proposed mounting reduces signal loss, especially in parts of the trajectory where its probability is the highest. This reduction effect appears especially for crystal oscillators with a low elevation angle g-sensitivity vector. The gyroscopic mounting influences frequency deviation or jitter caused by dynamic loads on replica carrier and affects the frequency locked loop (FLL) as the dominant tracking loop in highly dynamic GNSS receivers. In terms of steady-state load, the proposed mounting mostly reduces the frequency deviation below the one-sigma threshold of FLL (1σFLL). The mounting method can also reduce the frequency jitter caused by sinusoidal vibrations and reduces the probability of signal loss in parts of the trajectory where the other error sources accompany this vibration load. In the case of random vibration, which is the main disturbance source of FLL, gyroscopic mounting is even able to suppress the disturbances greater than the three-sigma threshold of FLL (3σFLL). In this way, signal tracking performance can be improved by the gyroscopic mounting method for highly dynamic GNSS receivers. PMID:26404286

  5. Mitochondria-endoplasmic reticulum choreography: structure and signaling dynamics.

    PubMed

    Pizzo, Paola; Pozzan, Tullio

    2007-10-01

    Mitochondria and endoplasmic reticulum (ER) have different roles in living cells but they interact both physically and functionally. A key aspect of the mitochondria-ER relationship is the modulation of Ca(2+) signaling during cell activation, which thus affects a variety of physiological processes. We focus here on the molecular aspects that control the dynamics of the organelle-organelle interaction and their relationship with Ca(2+) signals, also discussing the consequences that these phenomena have, not only for cell physiology but also in the control of cell death.

  6. Systematic Characterization of Dynamic Parameters of Intracellular Calcium Signals

    PubMed Central

    Mackay, Laurent; Mikolajewicz, Nicholas; Komarova, Svetlana V.; Khadra, Anmar

    2016-01-01

    Dynamic processes, such as intracellular calcium signaling, are hallmark of cellular biology. As real-time imaging modalities become widespread, a need for analytical tools to reliably characterize time-series data without prior knowledge of the nature of the recordings becomes more pressing. The goal of this study is to develop a signal-processing algorithm for MATLAB that autonomously computes the parameters characterizing prominent single transient responses (TR) and/or multi-peaks responses (MPR). The algorithm corrects for signal contamination and decomposes experimental recordings into contributions from drift, TRs, and MPRs. It subsequently provides numerical estimates for the following parameters: time of onset after stimulus application, activation time (time for signal to increase from 10 to 90% of peak), and amplitude of response. It also provides characterization of the (i) TRs by quantifying their area under the curve (AUC), response duration (time between 1/2 amplitude on ascent and descent of the transient), and decay constant of the exponential decay region of the deactivation phase of the response, and (ii) MPRs by quantifying the number of peaks, mean peak magnitude, mean periodicity, standard deviation of periodicity, oscillatory persistence (time between first and last discernable peak), and duty cycle (fraction of period during which system is active) for all the peaks in the signal, as well as coherent oscillations (i.e., deterministic spikes). We demonstrate that the signal detection performance of this algorithm is in agreement with user-mediated detection and that parameter estimates obtained manually and algorithmically are correlated. We then apply this algorithm to study how metabolic acidosis affects purinergic (P2) receptor-mediated calcium signaling in osteoclast precursor cells. Our results reveal that acidosis significantly attenuates the amplitude and AUC calcium responses at high ATP concentrations. Collectively, our data

  7. SIGNAL TRANSDUCTION. Membrane potential modulates plasma membrane phospholipid dynamics and K-Ras signaling.

    PubMed

    Zhou, Yong; Wong, Ching-On; Cho, Kwang-jin; van der Hoeven, Dharini; Liang, Hong; Thakur, Dhananiay P; Luo, Jialie; Babic, Milos; Zinsmaier, Konrad E; Zhu, Michael X; Hu, Hongzhen; Venkatachalam, Kartik; Hancock, John F

    2015-08-21

    Plasma membrane depolarization can trigger cell proliferation, but how membrane potential influences mitogenic signaling is uncertain. Here, we show that plasma membrane depolarization induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K-Ras, which is targeted to the plasma membrane by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes in phosphatidylserine and K-Ras plasma membrane organization occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in vivo and robustly amplify K-Ras-dependent mitogen-activated protein kinase (MAPK) signaling. Conversely, plasma membrane repolarization disrupts K-Ras nanoclustering and inhibits MAPK signaling. By responding to voltage-induced changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up the plasma membrane as a biological field-effect transistor, allowing membrane potential to control the gain in mitogenic signaling circuits.

  8. Unveiling Hidden Dynamics of Hippo Signalling: A Systems Analysis

    PubMed Central

    Shin, Sung-Young; Nguyen, Lan K.

    2016-01-01

    The Hippo signalling pathway has recently emerged as an important regulator of cell apoptosis and proliferation with significant implications in human diseases. In mammals, the pathway contains the core kinases MST1/2, which phosphorylate and activate LATS1/2 kinases. The pro-apoptotic function of the MST/LATS signalling axis was previously linked to the Akt and ERK MAPK pathways, demonstrating that the Hippo pathway does not act alone but crosstalks with other signalling pathways to coordinate network dynamics and cellular outcomes. These crosstalks were characterised by a multitude of complex regulatory mechanisms involving competitive protein-protein interactions and phosphorylation mediated feedback loops. However, how these different mechanisms interplay in different cellular contexts to drive the context-specific network dynamics of Hippo-ERK signalling remains elusive. Using mathematical modelling and computational analysis, we uncovered that the Hippo-ERK network can generate highly diverse dynamical profiles that can be clustered into distinct dose-response patterns. For each pattern, we offered mechanistic explanation that defines when and how the observed phenomenon can arise. We demonstrated that Akt displays opposing, dose-dependent functions towards ERK, which are mediated by the balance between the Raf-1/MST2 protein interaction module and the LATS1 mediated feedback regulation. Moreover, Ras displays a multi-functional role and drives biphasic responses of both MST2 and ERK activities; which are critically governed by the competitive protein interaction between MST2 and Raf-1. Our study represents the first in-depth and systematic analysis of the Hippo-ERK network dynamics and provides a concrete foundation for future studies. PMID:27527217

  9. The analyses of dynamic response and reliability of fuzzy-random truss under stationary stochastic excitation

    NASA Astrophysics Data System (ADS)

    Ma, Juan; Gao, Wei; Wriggers, Peter; Wu, Tao; Sahraee, Shahab

    2010-04-01

    A new two-factor method based on the probability and the fuzzy sets theory is used for the analyses of the dynamic response and reliability of fuzzy-random truss systems under the stationary stochastic excitation. Considering the fuzzy-randomness of the structural physical parameters and geometric dimensions simultaneously, the fuzzy-random correlation function matrix of structural displacement response in time domain and the fuzzy-random mean square values of structural dynamic response in frequency domain are developed by using the two-factor method, and the fuzzy numerical characteristics of dynamic responses are then derived. Based on numerical characteristics of structural fuzzy-random dynamic responses, the structural fuzzy-random dynamic reliability and its fuzzy numerical characteristic are obtained from the Poisson equation. The effects of the uncertainty of the structural parameters on structural dynamic response and reliability are illustrated via two engineering examples and some important conclusions are obtained.

  10. Fault diagnosis of motor drives using stator current signal analysis based on dynamic time warping

    NASA Astrophysics Data System (ADS)

    Zhen, D.; Wang, T.; Gu, F.; Ball, A. D.

    2013-01-01

    Electrical motor stator current signals have been widely used to monitor the condition of induction machines and their downstream mechanical equipment. The key technique used for current signal analysis is based on Fourier transform (FT) to extract weak fault sideband components from signals predominated with supply frequency component and its higher order harmonics. However, the FT based method has limitations such as spectral leakage and aliasing, leading to significant errors in estimating the sideband components. Therefore, this paper presents the use of dynamic time warping (DTW) to process the motor current signals for detecting and quantifying common faults in a downstream two-stage reciprocating compressor. DTW is a time domain based method and its algorithm is simple and easy to be embedded into real-time devices. In this study DTW is used to suppress the supply frequency component and highlight the sideband components based on the introduction of a reference signal which has the same frequency component as that of the supply power. Moreover, a sliding window is designed to process the raw signal using DTW frame by frame for effective calculation. Based on the proposed method, the stator current signals measured from the compressor induced with different common faults and under different loads are analysed for fault diagnosis. Results show that DTW based on residual signal analysis through the introduction of a reference signal allows the supply components to be suppressed well so that the fault related sideband components are highlighted for obtaining accurate fault detection and diagnosis results. In particular, the root mean square (RMS) values of the residual signal can indicate the differences between the healthy case and different faults under varying discharge pressures. It provides an effective and easy approach to the analysis of motor current signals for better fault diagnosis of the downstream mechanical equipment of motor drives in the time

  11. Interrogating the signaling dynamics of T cell activation with quantum dots

    NASA Astrophysics Data System (ADS)

    Warnement, Michael R.; Faley, Shannon L.; Wikswo, John P.; Rosenthal, Sandra J.

    2006-02-01

    We report the use of antibody-conjugated quantum dots (QDs) to monitor the expression dynamics of the membrane bound cytokine receptor interleukin-2 receptor-α (IL-2Rα) throughout the course of Jurkat T cell activation. Maximal receptor expression is observed 32-48 hours after activation, followed by a sharp decrease subsequent to 48 hours consistent with IL-2R internalization. Fluorescence microscopy, ELISA, and FACS analyses were used to verify controlled activation and specificity of QD labeling. Additionally, confocal microscopy demonstrated receptor internalization subsequent to expression and QD labeling. Antibody-conjugated QDs provide a convenient means to rapidly determine cell state and interrogate end products of cell signaling pathways. Interrogation of other signaling pathways can eventually be carried out in a similar manner upon identification of relevant membrane associated receptors. Ultimately, the multiplexing capabilities of QDs will allow the examination of several signaling pathways simultaneously and aid in toxin detection and discrimination.

  12. Comparisons of several aerodynamic methods for application to dynamic loads analyses

    NASA Technical Reports Server (NTRS)

    Kroll, R. I.; Miller, R. D.

    1976-01-01

    The results of a study are presented in which the applicability at subsonic speeds of several aerodynamic methods for predicting dynamic gust loads on aircraft, including active control systems, was examined and compared. These aerodynamic methods varied from steady state to an advanced unsteady aerodynamic formulation. Brief descriptions of the structural and aerodynamic representations and of the motion and load equations are presented. Comparisons of numerical results achieved using the various aerodynamic methods are shown in detail. From these results, aerodynamic representations for dynamic gust analyses are identified. It was concluded that several aerodynamic methods are satisfactory for dynamic gust analyses of configurations having either controls fixed or active control systems that primarily affect the low frequency rigid body aircraft response.

  13. Luminal Ca2+ dynamics during IP3R mediated signals

    NASA Astrophysics Data System (ADS)

    Lopez, Lucia F.; Ponce Dawson, Silvina

    2016-06-01

    The role of cytosolic Ca2+ on the kinetics of Inositol 1,4,5-triphosphate receptors (IP3Rs) and on the dynamics of IP3R-mediated Ca2+ signals has been studied at large both experimentally and by modeling. The role of luminal Ca2+ has not been investigated with that much detail although it has been found that it is relevant for signal termination in the case of Ca2+ release through ryanodine receptors. In this work we present the results of observing the dynamics of luminal and cytosolic Ca2+ simultaneously in Xenopus laevis oocytes. Combining observations and modeling we conclude that there is a rapid mechanism that guarantees the availability of free Ca2+ in the lumen even when a relatively large Ca2+ release is evoked. Comparing the dynamics of cytosolic and luminal Ca2+ during a release, we estimate that they are consistent with a 80% of luminal Ca2+ being buffered. The rapid availability of free luminal Ca2+ correlates with the observation that the lumen occupies a considerable volume in several regions across the images.

  14. Evolving from static to dynamic signals: evolutionary compensation between two communicative signals

    PubMed Central

    Martins, Emília P.; Ossip-Klein, Alison G.; Zúñiga-Vega, J. Jaime; García, Cuauhcihuatl Vital; Campos, Stephanie M.; Hews, Diana K.

    2015-01-01

    Signals that convey related information may impose selection on each other, creating evolutionary links between different components of the communicative repertoire. Here, we ask about the consequences of the evolutionary loss of one signal (a colour patch) on another (a motion display) in Sceloporus lizards. We present data on male lizards of four species: two pairs of sister taxa representing two independent evolutionary losses of the static colour patch (Sceloporus cozumelae and Sceloporus parvus; Sceloporus siniferus and Sceloporus merriami). Males of the two species that have undergone an evolutionary loss of blue-belly patches (S. cozumelae, S. siniferus) were less active than their blue-bellied sister taxa (S. parvus, S. merriami), consistent with the suggestion that the belly patches were lost to reduce conspicuousness of species with high predation pressure. In contrast, the headbob display appears to have become more, rather than less, conspicuous over evolutionary time. The colour patch is exhibited primarily during aggressive encounters, whereas headbob displays are multifunction signals used in several different contexts, including aggressive encounters. Males of species that have lost the colour patch produced more motion displays, and the structure of those motion displays were more similar to those produced during combat. In both evolutionary episodes, a static colour signal appears to have been replaced by dynamic motion displays that can be turned off in the presence of predators and other unwanted receivers. The predominant pattern is one of evolutionary compensation and interactions between multiple signals that convey related information. PMID:25892737

  15. Multiparticle collision dynamics for diffusion-influenced signaling pathways

    NASA Astrophysics Data System (ADS)

    Strehl, R.; Rohlf, K.

    2016-08-01

    An efficient yet accurate simulation method for modeling diffusion-influenced reaction networks is presented. The method extends existing reactive multiparticle collision dynamics by incorporating species-dependent diffusion coefficients, and developing theoretical expressions for the reactant-dependent diffusion control. This off-lattice particle-based mesoscopic simulation tool is particularly suited for problems in which detailed descriptions of particle trajectories and local reactions are required. Numerical simulations of an intracellular signaling pathway for bacterial chemotaxis are carried out to validate our approach, and to demonstrate its efficiency.

  16. Signalling protein complexes isolated from primary human skin-resident T cells can be analysed by Multiplex IP-FCM.

    PubMed

    Smith, Stephen E P; Neier, Steven C; Davis, Tessa R; Pittelkow, Mark R; Gil, Diana; Schrum, Adam G

    2014-04-01

    Studying signal transduction in skin-resident T cells (sr-T cells) can be limited by the small size of clinical biopsies. Here, we isolated sr-T cells from clinical samples and analysed signalling protein complexes by multiplex immunoprecipitation detected by flow cytometry (mIP-FCM). In samples from two independent donors, antigenic stimulation induced signalling proteins to join shared complexes that were observed in seven pairwise combinations among five proteins. This demonstrates that sr-T cells isolated from small clinical samples provide sufficient material for mIP-FCM-based analysis of signalling-induced protein complexes. We propose that this strategy may be useful for gaining improved mechanistic insight of sr-T cell signal transduction associated with dermatological disease.

  17. Promoter nucleosome dynamics regulated by signalling through the CTD code

    PubMed Central

    Materne, Philippe; Anandhakumar, Jayamani; Migeot, Valerie; Soriano, Ignacio; Yague-Sanz, Carlo; Hidalgo, Elena; Mignion, Carole; Quintales, Luis; Antequera, Francisco; Hermand, Damien

    2015-01-01

    The phosphorylation of the RNA polymerase II C-terminal domain (CTD) plays a key role in delineating transcribed regions within chromatin by recruiting histone methylases and deacetylases. Using genome-wide nucleosome mapping, we show that CTD S2 phosphorylation controls nucleosome dynamics in the promoter of a subset of 324 genes, including the regulators of cell differentiation ste11 and metabolic adaptation inv1. Mechanistic studies on these genes indicate that during gene activation a local increase of phospho-S2 CTD nearby the promoter impairs the phospho-S5 CTD-dependent recruitment of Set1 and the subsequent recruitment of specific HDACs, which leads to nucleosome depletion and efficient transcription. The early increase of phospho-S2 results from the phosphorylation of the CTD S2 kinase Lsk1 by MAP kinase in response to cellular signalling. The artificial tethering of the Lsk1 kinase at the ste11 promoter is sufficient to activate transcription. Therefore, signalling through the CTD code regulates promoter nucleosomes dynamics. DOI: http://dx.doi.org/10.7554/eLife.09008.001 PMID:26098123

  18. Characterizing rhodopsin signaling by EPR spectroscopy: from structure to dynamics.

    PubMed

    Van Eps, Ned; Caro, Lydia N; Morizumi, Takefumi; Ernst, Oliver P

    2015-09-26

    Electron paramagnetic resonance (EPR) spectroscopy, together with spin labeling techniques, has played a major role in the characterization of rhodopsin, the photoreceptor protein and G protein-coupled receptor (GPCR) in rod cells. Two decades ago, these biophysical tools were the first to identify transmembrane helical movements in rhodopsin upon photo-activation, a critical step in the study of GPCR signaling. EPR methods were employed to identify functional loop dynamics within rhodopsin, to measure light-induced millisecond timescale changes in rhodopsin conformation, to characterize the effects of partial agonists on the apoprotein opsin, and to study lipid interactions with rhodopsin. With the emergence of advanced pulsed EPR techniques, the stage was set to determine the amplitude of structural changes in rhodopsin and the dynamics in the rhodopsin signaling complexes. Work in this area has yielded invaluable information about mechanistic properties of GPCRs. Using EPR techniques, receptors are studied in native-like membrane environments and the effects of lipids on conformational equilibria can be explored. This perspective addresses the impact of EPR methods on rhodopsin and GPCR structural biology, highlighting historical discoveries made with spin labeling techniques, and outlining exciting new directions in the field.

  19. Signalling and the evolution of cooperative foraging in dynamic environments.

    PubMed

    Torney, Colin J; Berdahl, Andrew; Couzin, Iain D

    2011-09-01

    Understanding cooperation in animal social groups remains a significant challenge for evolutionary theory. Observed behaviours that benefit others but incur some cost appear incompatible with classical notions of natural selection; however, these behaviours may be explained by concepts such as inclusive fitness, reciprocity, intra-specific mutualism or manipulation. In this work, we examine a seemingly altruistic behaviour, the active recruitment of conspecifics to a food resource through signalling. Here collective, cooperative behaviour may provide highly nonlinear benefits to individuals, since group functionality has the potential to be far greater than the sum of the component parts, for example by enabling the effective tracking of a dynamic resource. We show that due to this effect, signalling to others is an evolutionarily stable strategy under certain environmental conditions, even when there is a cost associated to this behaviour. While exploitation is possible, in the limiting case of a sparse, ephemeral but locally abundant nutrient source, a given environmental profile will support a fixed number of signalling individuals. Through a quantitative analysis, this effective carrying capacity for cooperation is related to the characteristic length and time scales of the resource field.

  20. Dynamic binding of RBPJ is determined by Notch signaling status

    PubMed Central

    Castel, David; Mourikis, Philippos; Bartels, Stefanie J.J.; Brinkman, Arie B.; Tajbakhsh, Shahragim; Stunnenberg, Hendrik G.

    2013-01-01

    Notch signaling plays crucial roles in mediating cell fate choices in all metazoans largely by specifying the transcriptional output of one cell in response to a neighboring cell. The DNA-binding protein RBPJ is the principle effector of this pathway in mammals and, together with the transcription factor moiety of Notch (NICD), regulates the expression of target genes. The prevalent view presumes that RBPJ statically occupies consensus binding sites while exchanging repressors for activators in response to NICD. We present the first specific RBPJ chromatin immunoprecipitation and high-throughput sequencing study in mammalian cells. To dissect the mode of transcriptional regulation by RBPJ and identify its direct targets, whole-genome binding profiles were generated for RBPJ; its coactivator, p300; NICD; and the histone H3 modifications H3 Lys 4 trimethylation (H3K4me3), H3 Lys 4 monomethylation (H3K4me1), and histone H3 Lys 27 acetylation (H3K27ac) in myogenic cells under active or inhibitory Notch signaling conditions. Our results demonstrate dynamic binding of RBPJ in response to Notch activation at essentially all sites co-occupied by NICD. Additionally, we identify a distinct set of sites where RBPJ recruits neither NICD nor p300 and binds DNA statically, irrespective of Notch activity. These findings significantly modify our views on how RBPJ and Notch signaling mediate their activities and consequently impact on cell fate decisions. PMID:23651858

  1. Assessment of Tools and Data for System-Level Dynamic Analyses

    SciTech Connect

    Steven J. Piet; Nick R. Soelberg

    2011-06-01

    The only fuel cycle for which dynamic analyses and assessments are not needed is the null fuel cycle - no nuclear power. For every other concept, dynamic analyses are needed and can influence relative desirability of options. Dynamic analyses show how a fuel cycle might work during transitions from today's partial fuel cycle to something more complete, impact of technology deployments, location of choke points, the key time lags, when benefits can manifest, and how well parts of fuel cycles work together. This report summarizes the readiness of existing Fuel Cycle Technology (FCT) tools and data for conducting dynamic analyses on the range of options. VISION is the primary dynamic analysis tool. Not only does it model mass flows, as do other dynamic system analysis models, but it allows users to explore various potential constraints. The only fuel cycle for which constraints are not important are those in concept advocates PowerPoint presentations; in contrast, comparative analyses of fuel cycles must address what constraints exist and how they could impact performance. The most immediate tool need is extending VISION to the thorium/U233 fuel cycle. Depending on further clarification of waste management strategies in general and for specific fuel cycle candidates, waste management sub-models in VISION may need enhancement, e.g., more on 'co-flows' of non-fuel materials, constraints in waste streams, or automatic classification of waste streams on the basis of user-specified rules. VISION originally had an economic sub-model. The economic calculations were deemed unnecessary in later versions so it was retired. Eventually, the program will need to restore and improve the economics sub-model of VISION to at least the cash flow stage and possibly to incorporating cost constraints and feedbacks. There are multiple sources of data that dynamic analyses can draw on. In this report, 'data' means experimental data, data from more detailed theoretical or empirical

  2. Comparative survey of dynamic analyses of free-piston stirling engines

    SciTech Connect

    Kankam, M.D.; Rauch, J.S.

    1994-09-01

    This paper compares reported dynamic analyses for evaluating the steady-state response and stability of free-piston Stirling engine (FPSE) systems. Various analytical approaches are discussed to provide guidance on their salient features. Recommendations are made in the recommendations remarks for an approach which captures most of the inherent properties of the engine. Such an approach has the potential for yielding results which will closely match practical FPSE-load systems.

  3. Comparative survey of dynamic analyses of free-piston Stirling engines

    NASA Technical Reports Server (NTRS)

    Kankam, M. David; Rauch, Jeffrey S.

    1991-01-01

    Reported dynamics analyses for evaluating the steady-state response and stability of free-piston Stirling engine (FPSE) systems are compared. Various analytical approaches are discussed to provide guidance on their salient features. Recommendations are made in the recommendations remarks for an approach which captures most of the inherent properties of the engine. Such an approach has the potential for yielding results which will closely match practical FPSE-load systems.

  4. Use of operational analyses to study the dynamics of troposphere-stratosphere interactions in polar regions

    NASA Technical Reports Server (NTRS)

    Salstein, David A.; Rosen, Richard D.; Miller, Alvin J.

    1988-01-01

    Operational analyses produced by large weather centers have been used in the past to monitor various aspects of the general circulation as well as address dynamical questions. For a number years researchers have been monitoring National Meteorological Center (NMC) analyses at 100 millibars because it is the level from which stratospheric analyses are built. In particular, they closely examined the pressure-work term at that level which is an important parameter related to the forcing of the stratosphere by the troposphere. Rapid fluctuations typically seen in this quanity during the months of July-November, and similarly noted by Randel et al., (1987) may raise some concern about the quality of the analyses. Researchers investigated the behavior of the term mainly responsible for these variations, namely the eddy flux of heat, and furthermore have corroborated the presence of these variations in contemporaneous analyses produced by the European Centre for Medium Range Forecasts (ECMWF). Researchers demonstrated that fluctuations in standing eddy heat fluxes, related to the forcing of the stratosphere by the troposphere, agree in two largely independent meteorological analyses. Researchers believe, that these fluctuations are mostly real.

  5. Optimal BLS: Optimizing transit-signal detection for Keplerian dynamics

    NASA Astrophysics Data System (ADS)

    Ofir, Aviv

    2015-08-01

    Transit surveys, both ground- and space-based, have already accumulated a large number of light curves that span several years. We optimize the search for transit signals for both detection and computational efficiencies by assuming that the searched systems can be described by Keplerian, and propagating the effects of different system parameters to the detection parameters. Importnantly, we mainly consider the information content of the transit signal and not any specific algorithm - and use BLS (Kovács, Zucker, & Mazeh 2002) just as a specific example.We show that the frequency information content of the light curve is primarily determined by the duty cycle of the transit signal, and thus the optimal frequency sampling is found to be cubic and not linear. Further optimization is achieved by considering duty-cycle dependent binning of the phased light curve. By using the (standard) BLS, one is either fairly insensitive to long-period planets or less sensitive to short-period planets and computationally slower by a significant factor of ~330 (for a 3 yr long dataset). We also show how the physical system parameters, such as the host star's size and mass, directly affect transit detection. This understanding can then be used to optimize the search for every star individually.By considering Keplerian dynamics explicitly rather than implicitly one can optimally search the transit signal parameter space. The presented Optimal BLS enhances the detectability of both very short and very long period planets, while allowing such searches to be done with much reduced resources and time. The Matlab/Octave source code for Optimal BLS is made available.

  6. Single-Cell Analyses Reveal That KISS1R-Expressing Cells Undergo Sustained Kisspeptin-Induced Signaling That Is Dependent upon An Influx of Extracellular Ca2+

    PubMed Central

    Pampillo, Macarena; Min, Le; Kaiser, Ursula B.; Bhattacharya, Moshmi

    2012-01-01

    The kisspeptin receptor (KISS1R) is a Gαq/11-coupled seven-transmembrane receptor activated by a group of peptides referred to as kisspeptins (Kps). The Kp/KISS1R signaling system is a powerful regulator of GnRH secretion, and inactivating mutations in this system are associated with hypogonadotropic hypogonadism. A recent study revealed that Kp triggers prolonged signaling; not from the inability of the receptor to undergo rapid desensitization, but instead from the maintenance of a dynamic and active pool of KISS1R at the cell surface. To investigate this further, we hypothesized that if a dynamic pool of receptor is maintained at the cell surface for a protracted period, chronic Kp-10 treatment would trigger the sustained activation of Gαq/11 as evidenced through the prolonged activation of phospholipase C, protein kinase C, and prolonged mobilization of intracellular Ca2+. Through single-cell analyses, we tested our hypothesis in human embryonic kidney (HEK) 293 cells and found that was indeed the case. We subsequently determined that prolonged KISS1R signaling was not a phenomenon specific to HEK 293 cells but is likely a conserved property of KISS1R-expressing cells because evidence of sustained KISS1R signaling was also observed in the GT1–7 GnRH neuronal and Chinese hamster ovary cell lines. While exploring the regulation of prolonged KISS1R signaling, we identified a critical role for extracellular Ca2+. We found that although free intracellular Ca2+, primarily derived from intracellular stores, was sufficient to trigger the acute activation of a major KISS1R secondary effector, protein kinase C, it was insufficient to sustain chronic KISS1R signaling; instead extracellular Ca2+ was absolutely required for this. PMID:23070548

  7. Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses

    PubMed Central

    Toyama, Yuki; Kano, Hanaho; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

    2017-01-01

    Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation. PMID:28223697

  8. Analysis of Signaling Endosome Composition and Dynamics Using SILAC in Embryonic Stem Cell-Derived Neurons*

    PubMed Central

    Debaisieux, Solène; Encheva, Vesela; Chakravarty, Probir; Snijders, Ambrosius P.; Schiavo, Giampietro

    2016-01-01

    Neurons require efficient transport mechanisms such as fast axonal transport to ensure neuronal homeostasis and survival. Neurotrophins and their receptors are conveyed via fast axonal retrograde transport of signaling endosomes to the soma, where they elicit transcriptional responses. Despite the essential roles of signaling endosomes in neuronal differentiation and survival, little is known about their molecular identity, dynamics, and regulation. Gaining a better mechanistic understanding of these organelles and their kinetics is crucial, given the growing evidence linking vesicular trafficking deficits to neurodegeneration. Here, we exploited an affinity purification strategy using the binding fragment of tetanus neurotoxin (HCT) conjugated to monocrystalline iron oxide nanoparticles (MIONs), which in motor neurons, is transported in the same carriers as neurotrophins and their receptors. To quantitatively assess the molecular composition of HCT-containing signaling endosomes, we have developed a protocol for triple Stable Isotope Labeling with Amino acids in Cell culture (SILAC) in embryonic stem cell-derived motor neurons. After HCT internalization, retrograde carriers were magnetically isolated at different time points and subjected to mass-spectrometry and Gene Ontology analyses. This purification strategy is highly specific, as confirmed by the presence of essential regulators of fast axonal transport in the make-up of these organelles. Our results indicate that signaling endosomes undergo a rapid maturation with the acquisition of late endosome markers following a specific time-dependent kinetics. Strikingly, signaling endosomes are specifically enriched in proteins known to be involved in neurodegenerative diseases and neuroinfection. Moreover, we highlighted the presence of novel components, whose precise temporal recruitment on signaling endosomes might be essential for proper sorting and/or transport of these organelles. This study provides the first

  9. Quick and inexpensive paraffin-embedding method for dynamic bone formation analyses

    PubMed Central

    Porter, Amy; Irwin, Regina; Miller, Josselyn; Horan, Daniel J.; Robling, Alexander G.; McCabe, Laura R.

    2017-01-01

    We have developed a straightforward method that uses paraffin-embedded bone for undemineralized thin sectioning, which is amenable to subsequent dynamic bone formation measurements. Bone has stiffer material properties than paraffin, and therefore has hereforto usually been embedded in plastic blocks, cured and sectioned with a tungsten carbide knife to obtain mineralized bone sections for dynamic bone formation measures. This process is expensive and requires special equipment, experienced personnel, and time for the plastic to penetrate the bone and cure. Our method utilizes a novel way to prepare mineralized bone that increases its compliance so that it can be embedded and easily section in paraffin blocks. The approach is simple, quick, and costs less than 10% of the price for plastic embedded bone sections. While not effective for static bone measures, this method allows dynamic bone analyses to be readily performed in laboratories worldwide which might not otherwise have access to traditional (plastic) equipment and expertise. PMID:28198415

  10. A bead-based western for high-throughput cellular signal transduction analyses

    PubMed Central

    Treindl, Fridolin; Ruprecht, Benjamin; Beiter, Yvonne; Schultz, Silke; Döttinger, Anette; Staebler, Annette; Joos, Thomas O.; Kling, Simon; Poetz, Oliver; Fehm, Tanja; Neubauer, Hans; Kuster, Bernhard; Templin, Markus F.

    2016-01-01

    Dissecting cellular signalling requires the analysis of large number of proteins. The DigiWest approach we describe here transfers the western blot to a bead-based microarray platform. By combining gel-based protein separation with immobilization on microspheres, hundreds of replicas of the initial blot are created, thus enabling the comprehensive analysis of limited material, such as cells collected by laser capture microdissection, and extending traditional western blotting to reach proteomic scales. The combination of molecular weight resolution, sensitivity and signal linearity on an automated platform enables the rapid quantification of hundreds of specific proteins and protein modifications in complex samples. This high-throughput western blot approach allowed us to identify and characterize alterations in cellular signal transduction that occur during the development of resistance to the kinase inhibitor Lapatinib, revealing major changes in the activation state of Ephrin-mediated signalling and a central role for p53-controlled processes. PMID:27659302

  11. Static and dynamic stress analyses of the prototype high head Francis runner based on site measurement

    NASA Astrophysics Data System (ADS)

    Huang, X.; Oram, C.; Sick, M.

    2014-03-01

    More efforts are put on hydro-power to balance voltage and frequency within seconds for primary control in modern smart grids. This requires hydraulic turbines to run at off-design conditions. especially at low load or speed-no load. Besides. the tendency of increasing power output and decreasing weight of the turbine runners has also led to the high level vibration problem of the runners. especially high head Francis runners. Therefore. it is important to carry out the static and dynamic stress analyses of prototype high head Francis runners. This paper investigates the static and dynamic stresses on the prototype high head Francis runner based on site measurements and numerical simulations. The site measurements are performed with pressure transducers and strain gauges. Based on the measured results. computational fluid dynamics (CFD) simulations for the flow channel from stay vane to draft tube cone are performed. Static pressure distributions and dynamic pressure pulsations caused by rotor-stator interaction (RSI) are obtained under various operating conditions. With the CFD results. static and dynamic stresses on the runner at different operating points are calculated by means of the finite element method (FEM). The agreement between simulation and measurement is analysed with linear regression method. which indicates that the numerical result agrees well with that of measurement. Furthermore. the maximum static and dynamic stresses on the runner blade are obtained at various operating points. The relations of the maximum stresses and the power output are discussed in detail. The influences of the boundary conditions on the structural behaviour of the runner are also discussed.

  12. Dynamic neural activity during stress signals resilient coping

    PubMed Central

    Sinha, Rajita; Lacadie, Cheryl M.; Constable, R. Todd; Seo, Dongju

    2016-01-01

    Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

  13. Analysing animal social network dynamics: the potential of stochastic actor-oriented models.

    PubMed

    Fisher, David N; Ilany, Amiyaal; Silk, Matthew J; Tregenza, Tom

    2017-03-01

    Animals are embedded in dynamically changing networks of relationships with conspecifics. These dynamic networks are fundamental aspects of their environment, creating selection on behaviours and other traits. However, most social network-based approaches in ecology are constrained to considering networks as static, despite several calls for such analyses to become more dynamic. There are a number of statistical analyses developed in the social sciences that are increasingly being applied to animal networks, of which stochastic actor-oriented models (SAOMs) are a principal example. SAOMs are a class of individual-based models designed to model transitions in networks between discrete time points, as influenced by network structure and covariates. It is not clear, however, how useful such techniques are to ecologists, and whether they are suited to animal social networks. We review the recent applications of SAOMs to animal networks, outlining findings and assessing the strengths and weaknesses of SAOMs when applied to animal rather than human networks. We go on to highlight the types of ecological and evolutionary processes that SAOMs can be used to study. SAOMs can include effects and covariates for individuals, dyads and populations, which can be constant or variable. This allows for the examination of a wide range of questions of interest to ecologists. However, high-resolution data are required, meaning SAOMs will not be useable in all study systems. It remains unclear how robust SAOMs are to missing data and uncertainty around social relationships. Ultimately, we encourage the careful application of SAOMs in appropriate systems, with dynamic network analyses likely to prove highly informative. Researchers can then extend the basic method to tackle a range of existing questions in ecology and explore novel lines of questioning.

  14. Variational Assimilation of Global Microwave Rainfall Retrievals: Physical and Dynamical Impact on GEOS Analyses and Forecasts

    NASA Technical Reports Server (NTRS)

    Lin, Xin; Zhang, Sara Q.; Hou, Arthur Y.

    2006-01-01

    Global microwave rainfall retrievals from a 5-satellite constellation, including TMI from TRMM, SSWI from DMSP F13, F14 and F15, and AMSR-E from EOS-AQUA, are assimilated into the NASA Goddard Earth Observing System (GEOS) Data Assimilation System (DAS) using a 1-D variational continuous assimilation (VCA) algorithm. The physical and dynamical impact of rainfall assimilation on GEOS analyses and forecasts is examined at various temporal and spatial scales. This study demonstrates that the 1-D VCA algorithm, which was originally developed and evaluated for rainfall assimilations over tropical oceans, can effectively assimilate satellite microwave rainfall retrievals and improve GEOS analyses over both the Tropics and the extratropics where the atmospheric processes are dominated by different large-scale dynamics and moist physics, and also over the land, where rainfall estimates from passive microwave radiometers are believed to be less accurate. Results show that rainfall assimilation renders the GEOS analysis physically and dynamically more consistent with the observed precipitation at the monthly-mean and 6-hour time scales. Over regions where the model precipitation tends to misbehave in distinctly different rainy regimes, the 1-D VCA algorithm, by compensating for errors in the model s moist time-tendency in a 6-h analysis window, is able to bring the rainfall analysis closer to the observed. The radiation and cloud fields also tend to be in better agreement with independent satellite observations in the rainfall-assimilation m especially over regions where rainfall analyses indicate large improvements. Assimilation experiments with and without rainfall data for a midlatitude frontal system clearly indicates that the GEOS analysis is improved through changes in the thermodynamic and dynamic fields that respond to the rainfall assimilation. The synoptic structures of temperature, moisture, winds, divergence, and vertical motion, as well as vorticity are more

  15. Dynamic kisspeptin receptor trafficking modulates kisspeptin-mediated calcium signaling.

    PubMed

    Min, Le; Soltis, Kathleen; Reis, Ana Claudia S; Xu, Shuyun; Kuohung, Wendy; Jain, Manisha; Carroll, Rona S; Kaiser, Ursula B

    2014-01-01

    Kisspeptin receptor (KISS1R) signaling plays a critical role in the regulation of reproduction. We investigated the role of kisspeptin-stimulated KISS1R internalization, recycling, and degradation in the modulation of KISS1R signaling. Kisspeptin stimulation of Chinese hamster ovary or GT1-7 cells expressing KISS1R resulted in a biphasic increase in intracellular Ca(2+) ([Ca(2+)]i), with a rapid acute increase followed by a more sustained second phase. In contrast, stimulation of the TRH receptor, another Gq/11-coupled receptor, resulted in a much smaller second-phase [Ca(2+)]i response. The KISS1R-mediated second-phase [Ca(2+)]i response was abolished by removal of kisspeptin from cell culture medium. Notably, the second-phase [Ca(2+)]i response was also inhibited by dynasore, brefeldin A, and phenylarsine oxide, which inhibit receptor internalization and recycling, suggesting that KISS1R trafficking contributes to the sustained [Ca(2+)]i response. We further demonstrated that KISS1R undergoes dynamic ligand-dependent and -independent recycling. We next investigated the fate of the internalized kisspeptin-KISS1R complex. Most internalized kisspeptin was released extracellularly in degraded form within 1 hour, suggesting rapid processing of the internalized kisspeptin-KISS1R complex. Using a biotinylation assay, we demonstrated that degradation of cell surface KISS1R was much slower than that of the internalized ligand, suggesting dissociated processing of the internalized kisspeptin-KISS1R complex. Taken together, our results suggest that the sustained calcium response to kisspeptin is dependent on the continued presence of extracellular ligand and is the result of dynamic KISS1R trafficking.

  16. Dynamic protein interaction networks and new structural paradigms in signaling

    PubMed Central

    Csizmok, Veronika; Follis, Ariele Viacava; Kriwacki, Richard W.; Forman-Kay, Julie D.

    2017-01-01

    Understanding signaling and other complex biological processes requires elucidating the critical roles of intrinsically disordered proteins and regions (IDPs/IDRs), which represent ~30% of the proteome and enable unique regulatory mechanisms. In this review we describe the structural heterogeneity of disordered proteins that underpins these mechanisms and the latest progress in obtaining structural descriptions of ensembles of disordered proteins that are needed for linking structure and dynamics to function. We describe the diverse interactions of IDPs that can have unusual characteristics such as “ultrasensitivity” and “regulated folding and unfolding”. We also summarize the mounting data showing that large-scale assembly and protein phase separation occurs within a variety of signaling complexes and cellular structures. In addition, we discuss efforts to therapeutically target disordered proteins with small molecules. Overall, we interpret the remodeling of disordered state ensembles due to binding and post-translational modifications within an expanded framework for allostery that provides significant insights into how disordered proteins transmit biological information. PMID:26922996

  17. Dynamic conformal arc therapy: Transmitted signal in vivo dosimetry

    SciTech Connect

    Piermattei, Angelo; Stimato, Gerardina; Gaudino, Diego; Ramella, Sara; D'Angelillo, Rolando Maria; Cellini, Francesco; Trodella, Lucio; D'Onofrio, Guido; Grimaldi, Luca; Cilla, Savino; Fidanzio, Andrea; Placidi, Elisa; Azario, Luigi

    2008-05-15

    A method for the determination of the in vivo isocenter dose, D{sub iso}, has been applied to the dynamic conformal arc therapy (DCAT) for thoracic tumors. The method makes use of the transmitted signal, S{sub t,{alpha}}, measured at different gantry angles, {alpha}, by a small ion chamber positioned on the electronic portal imaging device. The in vivo method is implemented by a set of correlation functions obtained by the ratios between the transmitted signal and the midplane dose in a solid phantom, irradiated by static fields. The in vivo dosimetry at the isocenter for the DCAT requires the convolution between the signals , S{sub t,{alpha}}, and the dose reconstruction factors, C{sub {alpha}}, that depend on the patient's anatomy and on its tissue inhomogeneities along the beam central axis in the {alpha} direction. The C{sub {alpha}} factors are obtained by processing the patient's computed tomography scan. The method was tested by taking measurements in a cylindrical phantom and in a Rando Alderson phantom. The results show that the difference between the convolution calculations and the phantom measurements is within {+-}2%. The in vivo dosimetry of the stereotactic DCAT for six lung tumors, irradiated with three or four arcs, is reported. The isocenter dose up to 17 Gy per therapy fraction was delivered on alternating days for three fractions. The agreement obtained in this pilot study between the total in vivo dose D{sub iso} and the planned dose D{sub iso,TPS} at the isocenter is {+-}4%. The method has been applied on the DCAT obtaining a more extensive monitoring of possible systematic errors, the effect of which can invalidate the current therapy which uses a few high-dose fractions.

  18. Development of microbial-enzyme-mediated decomposition model parameters through steady-state and dynamic analyses

    SciTech Connect

    Wang, Gangsheng; Post, Wilfred M; Mayes, Melanie

    2013-01-01

    We developed a Microbial-ENzyme-mediated Decomposition (MEND) model, based on the Michaelis-Menten kinetics, that describes the dynamics of physically defined pools of soil organic matter (SOC). These include particulate, mineral-associated, dissolved organic matter (POC, MOC, and DOC, respectively), microbial biomass, and associated exoenzymes. The ranges and/or distributions of parameters were determined by both analytical steady-state and dynamic analyses with SOC data from the literature. We used an improved multi-objective parameter sensitivity analysis (MOPSA) to identify the most important parameters for the full model: maintenance of microbial biomass, turnover and synthesis of enzymes, and carbon use efficiency (CUE). The model predicted an increase of 2 C (baseline temperature =12 C) caused the pools of POC-Cellulose, MOC, and total SOC to increase with dynamic CUE and decrease with constant CUE, as indicated by the 50% confidence intervals. Regardless of dynamic or constant CUE, the pool sizes of POC, MOC, and total SOC varied from 8% to 8% under +2 C. The scenario analysis using a single parameter set indicates that higher temperature with dynamic CUE might result in greater net increases in both POC-Cellulose and MOC pools. Different dynamics of various SOC pools reflected the catalytic functions of specific enzymes targeting specific substrates and the interactions between microbes, enzymes, and SOC. With the feasible parameter values estimated in this study, models incorporating fundamental principles of microbial-enzyme dynamics can lead to simulation results qualitatively different from traditional models with fast/slow/passive pools.

  19. Improved Protein Arrays for Quantitative Systems Analysis of the Dynamics of Signaling Pathway Interactions

    SciTech Connect

    YANG, CHIN-RANG

    2013-12-11

    Astronauts and workers in nuclear plants who repeatedly exposed to low doses of ionizing radiation (IR, <10 cGy) are likely to incur specific changes in signal transduction and gene expression in various tissues of their body. Remarkable advances in high throughput genomics and proteomics technologies enable researchers to broaden their focus from examining single gene/protein kinetics to better understanding global gene/protein expression profiling and biological pathway analyses, namely Systems Biology. An ultimate goal of systems biology is to develop dynamic mathematical models of interacting biological systems capable of simulating living systems in a computer. This Glue Grant is to complement Dr. Boothman’s existing DOE grant (No. DE-FG02-06ER64186) entitled “The IGF1/IGF-1R-MAPK-Secretory Clusterin (sCLU) Pathway: Mediator of a Low Dose IR-Inducible Bystander Effect” to develop sensitive and quantitative proteomic technology that suitable for low dose radiobiology researches. An improved version of quantitative protein array platform utilizing linear Quantum dot signaling for systematically measuring protein levels and phosphorylation states for systems biology modeling is presented. The signals are amplified by a confocal laser Quantum dot scanner resulting in ~1000-fold more sensitivity than traditional Western blots and show the good linearity that is impossible for the signals of HRP-amplification. Therefore this improved protein array technology is suitable to detect weak responses of low dose radiation. Software is developed to facilitate the quantitative readout of signaling network activities. Kinetics of EGFRvIII mutant signaling was analyzed to quantify cross-talks between EGFR and other signaling pathways.

  20. Dynamics, stability, and control analyses of flapping wing micro-air vehicles

    NASA Astrophysics Data System (ADS)

    Orlowski, Christopher T.; Girard, Anouck R.

    2012-05-01

    The paper presents an overview of the various analyses of flight dynamics, stability, and control of flapping wing micro-air vehicles available in the literature. The potential benefits of flapping wing micro-air vehicles for civil, military, and search and rescue operations are numerous. The majority of the flight dynamics research involves the standard aircraft (6DOF) equations of motion, although a growth is evident in examining the multibody flight dynamics models of flapping wing micro-air vehicles. The stability of flapping wing micro-air vehicles is largely studied in the vicinity of hover and forward flight. The majority of stability studies focus on linear, time-invariant stability in the vicinity of reference flight conditions, such as hover or forward flight. The consistent result is that flapping wing micro-air vehicles are unstable in an open loop setting. The unstable result is based on linear and nonlinear stability analyses. Control has been demonstrated for hovering and forward flight through various methods, both linear and nonlinear in nature. The entirety of reported research into the stability and control of flapping wing micro-air vehicles has neglected the mass effects of the wings on the position and orientation of the central body. Successful control of a flapping wing micro-air vehicle, with the wings' mass effects included, is still an open research area.

  1. Observation of Wetland Dynamics with Global Navigation Satellite Signals Reflectometry

    NASA Astrophysics Data System (ADS)

    Zuffada, C.; Shah, R.; Nghiem, S. V.; Cardellach, E.; Chew, C. C.

    2015-12-01

    Wetland dynamics is crucial to changes in both atmospheric methane and terrestrial water storage. The Intergovernmental Panel on Climate Change's Fifth Assessment Report (IPCC AR5) highlights the role of wetlands as a key driver of methane (CH4) emission, which is more than one order of magnitude stronger than carbon dioxide as a greenhouse gas in the centennial time scale. Among the multitude of methane emission sources (hydrates, livestock, rice cultivation, freshwaters, landfills and waste, fossil fuels, biomass burning, termites, geological sources, and soil oxidation), wetlands constitute the largest contributor with the widest uncertainty range of 177-284 Tg(CH4) yr-1 according to the IPCC estimate. Wetlands are highly susceptible to climate change that might lead to wetland collapse. Such wetland destruction would decrease the terrestrial water storage capacity and thus contribute to sea level rise, consequently exacerbating coastal flooding problems. For both methane change and water storage change, wetland dynamics is a crucial factor with the largest uncertainty. Nevertheless, a complete and consistent map of global wetlands still needs to be obtained as the Ramsar Convention calls for a wetlands inventory and impact assessment. We develop a new method for observations of wetland change using Global Navigation Satellite Signals Reflectometry (GNSS-R) signatures for global wetland mapping in synergy with the existing capability, not only as a static inventory but also as a temporal dataset, to advance the capability for monitoring the dynamics of wetland extent relevant to addressing the science issues of CH4 emission change and terrestrial water storage change. We will demonstrate the capability of the new GNSS-R method over a rice field in the Ebro Delta wetland in Spain.

  2. Regulation of neuronal PKA signaling through AKAP targeting dynamics.

    PubMed

    Dell'Acqua, Mark L; Smith, Karen E; Gorski, Jessica A; Horne, Eric A; Gibson, Emily S; Gomez, Lisa L

    2006-07-01

    region that binds phosphatidylinositol-4,5-bisphosphate (PIP(2)), F-actin, and actin-linked cadherin adhesion molecules. Thus, anchoring of PKA and CaN as well as physical linkage of the AKAP to both cadherin-cytoskeletal and MAGUK-receptor complexes could play roles in coordinating changes in synaptic structure and receptor signaling functions underlying plasticity. Importantly, we provide evidence showing that NMDAR-CaN signaling pathways implicated in AMPAR regulation during LTD lead to a disruption of AKAP79/150 interactions with actin, MAGUKs, and cadherins and lead to a loss of the AKAP and anchored PKA from postsynapses. Our studies thus far indicate that this AKAP79/150 translocation depends on activation of CaN, F-actin reorganization, and possibly Ca(2+)-CaM binding to the N-terminal basic regions. Importantly, this tranlocation of the AKAP79/150-PKA complex from spines may shift the balance of PKA kinase and CaN/PP1 phosphatase activity at the postsynapse in favor of the phosphatases. This loss of PKA could then promote actions of CaN and PP1 during induction of LTD including maintaining AMPAR dephosphorylation, promoting AMPAR endocytosis, and preventing AMPAR recycling. Overall, these findings challenge the accepted notion that AKAPs are static anchors that position signaling proteins near fixed target substrates and instead suggest that AKAPs can function in more dynamic manners to regulate local signaling events.

  3. Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling.

    PubMed

    Hardeland, Rüdiger; Madrid, Juan Antonio; Tan, Dun-Xian; Reiter, Russel J

    2012-03-01

    Evidence is accumulating regarding the importance of circadian core oscillators, several associated factors, and melatonin signaling in the maintenance of health. Dysfunction of endogenous clocks, melatonin receptor polymorphisms, age- and disease-associated declines of melatonin likely contribute to numerous diseases including cancer, metabolic syndrome, diabetes type 2, hypertension, and several mood and cognitive disorders. Consequences of gene silencing, overexpression, gene polymorphisms, and deviant expression levels in diseases are summarized. The circadian system is a complex network of central and peripheral oscillators, some of them being relatively independent of the pacemaker, the suprachiasmatic nucleus. Actions of melatonin on peripheral oscillators are poorly understood. Various lines of evidence indicate that these clocks are also influenced or phase-reset by melatonin. This includes phase differences of core oscillator gene expression under impaired melatonin signaling, effects of melatonin and melatonin receptor knockouts on oscillator mRNAs or proteins. Cross-connections between melatonin signaling pathways and oscillator proteins, including associated factors, are discussed in this review. The high complexity of the multioscillator system comprises alternate or parallel oscillators based on orthologs and paralogs of the core components and a high number of associated factors with varying tissue-specific importance, which offers numerous possibilities for interactions with melatonin. It is an aim of this review to stimulate research on melatonin signaling in peripheral tissues. This should not be restricted to primary signal molecules but rather include various secondarily connected pathways and discriminate between direct effects of the pineal indoleamine at the target organ and others mediated by modulation of oscillators.

  4. Spatial and temporal analyses of geothermal climate signals: Implications for borehole paleoclimatology

    NASA Astrophysics Data System (ADS)

    Smerdon, Jason E.

    Inversions of subsurface temperature profiles to reconstruct ground surface temperature (GST) histories have been widely used as indicators of paleoclimate. These reconstructions assume that heat transport within the subsurface is conductive. Climatic interpretations of GST reconstructions also assume that GST is strongly coupled to surface air temperature (SAT) on timescales of decades and longer. I examine these two assumptions using records of SAT and subsurface temperature time series from Fargo, North Dakota; Prague, Czech Republic; Cape Henlopen State Park, Delaware; and Cape Hatteras National Seashore, North Carolina. These records comprise intra-daily observations that span parts of one or two decades. The characteristics of downward-propagating annual temperature signals at each site clearly indicate that heat transport in the subsurface can be described as one-dimensional conduction in a homogeneous medium. Extrapolations of subsurface observations to the ground surface yield estimates of annual GST signals, and allow comparisons to annual SAT signals. All annual GST signals are modestly attenuated and negligibly phase shifted relative to SAT. Relationships between GST and SAT are further explored on daily, seasonal, and annual timescales to identify and characterize the principal meteorological factors that lead to differences between GST and SAT. I compare subsurface temperature observations to calculations from a conductive subsurface model driven with daily SAT as the surface boundary condition and show daily differences exist between observed and modeled subsurface temperatures. Year-to-year spectral decompositions of daily SAT and subsurface temperature time series are also analyzed. Dissimilarities exist between annual amplitudes of GST and SAT signals. These amplitude differences partition into summer and winter seasons and can lead to mean annual GST that is either cooler or warmer than SAT. Additionally, the differences between mean annual GST

  5. Static and dynamic theoretical analyses of a scanning tip on suspended graphene surface

    NASA Astrophysics Data System (ADS)

    Yu, Yan-Zi; Guo, Jian-Gang

    2016-08-01

    Recent research progress shows that graphene exhibits distinct adhesion and friction behaviors. In the paper, the static and dynamic analyses of a diamond tip sliding on suspended graphene surface are conducted via theoretical and numerical research methods, and the adhesion and friction properties between them are investigated. The analytical expression of interaction potential between a diamond tip and graphene surface is derived based on the interatomic pairwise potential, and then, the lateral and normal interaction forces are calculated. The equilibrium heights and adhesion energy of the diamond tip are calculated on three particular sites of graphene surface. The influence of vertical distance between the tip and graphene surface is studied on the maximum static frictional force and initial velocity of tip. What is more, the influence of scanning velocity and damping are also analyzed on the frictional force and dynamic behaviors of the scanning tip, and the "stick-slip" phenomenon is observed and discussed by the numerical calculation.

  6. Evolutionary dynamics of influenza A nucleoprotein (NP) lineages revealed by large-scale sequence analyses.

    PubMed

    Xu, Jianpeng; Christman, Mary C; Donis, Ruben O; Lu, Guoqing

    2011-12-01

    Influenza A viral nucleoprotein (NP) plays a critical role in virus replication and host adaptation, however, the underlying molecular evolutionary dynamics of NP lineages are less well-understood. In this study, large-scale analyses of 5094 NP nucleotide sequences revealed eight distinct evolutionary lineages, including three host-specific lineages (human, classical swine and equine), two cross-host lineages (Eurasian avian-like swine and swine-origin human pandemic H1N1 2009) and three geographically isolated avian lineages (Eurasian, North American and Oceanian). The average nucleotide substitution rate of the NP lineages was estimated to be 2.4 × 10(-3) substitutions per site per year, with the highest value observed in pandemic H1N1 2009 (3.4 × 10(-3)) and the lowest in equine (0.9 × 10(-3)). The estimated time of most recent common ancestor (TMRCA) for each lineage demonstrated that the earliest human lineage was derived around 1906, and the latest pandemic H1N1 2009 lineage dated back to December 17, 2008. A marked time gap was found between the times when the viruses emerged and were first sampled, suggesting the crucial role for long-term surveillance of newly emerging viruses. The selection analyses showed that human lineage had six positive selection sites, whereas pandemic H1N1 2009, classical swine, Eurasian avian and Eurasian swine had only one or two sites. Protein structure analyses revealed several positive selection sites located in epitope regions or host adaptation regions, indicating strong adaptation to host immune system pressures in influenza viruses. Along with previous studies, this study provides new insights into the evolutionary dynamics of influenza A NP lineages. Further lineage analyses of other gene segments will allow better understanding of influenza A virus evolution and assist in the improvement of global influenza surveillance.

  7. Insulin signaling in type 2 diabetes: experimental and modeling analyses reveal mechanisms of insulin resistance in human adipocytes.

    PubMed

    Brännmark, Cecilia; Nyman, Elin; Fagerholm, Siri; Bergenholm, Linnéa; Ekstrand, Eva-Maria; Cedersund, Gunnar; Strålfors, Peter

    2013-04-05

    Type 2 diabetes originates in an expanding adipose tissue that for unknown reasons becomes insulin resistant. Insulin resistance reflects impairments in insulin signaling, but mechanisms involved are unclear because current research is fragmented. We report a systems level mechanistic understanding of insulin resistance, using systems wide and internally consistent data from human adipocytes. Based on quantitative steady-state and dynamic time course data on signaling intermediaries, normally and in diabetes, we developed a dynamic mathematical model of insulin signaling. The model structure and parameters are identical in the normal and diabetic states of the model, except for three parameters that change in diabetes: (i) reduced concentration of insulin receptor, (ii) reduced concentration of insulin-regulated glucose transporter GLUT4, and (iii) changed feedback from mammalian target of rapamycin in complex with raptor (mTORC1). Modeling reveals that at the core of insulin resistance in human adipocytes is attenuation of a positive feedback from mTORC1 to the insulin receptor substrate-1, which explains reduced sensitivity and signal strength throughout the signaling network. Model simulations with inhibition of mTORC1 are comparable with experimental data on inhibition of mTORC1 using rapamycin in human adipocytes. We demonstrate the potential of the model for identification of drug targets, e.g. increasing the feedback restores insulin signaling, both at the cellular level and, using a multilevel model, at the whole body level. Our findings suggest that insulin resistance in an expanded adipose tissue results from cell growth restriction to prevent cell necrosis.

  8. The importance of replicating genomic analyses to verify phylogenetic signal for recently evolved lineages.

    PubMed

    Fraser, Ceridwen I; McGaughran, Angela; Chuah, Aaron; Waters, Jonathan M

    2016-08-01

    Genomewide SNP data generated by nontargeted methods such as RAD and GBS are increasingly being used in phylogenetic and phylogeographic analyses. When these methods are used in the absence of a reference genome, however, little is known about the locations and evolution of the SNPs. In using such data to address phylogenetic questions, researchers risk drawing false conclusions, particularly if a representative number of SNPs is not obtained. Here, we empirically test the robustness of phylogenetic inference based on SNP data for closely related lineages. We conducted a genomewide analysis of 75 712 SNPs, generated via GBS, of southern bull-kelp (Durvillaea). Durvillaea chathamensis co-occurs with D. antarctica on Chatham Island, but the two species have previously been found to be so genetically similar that the status of the former has been questioned. Our results show that D. chathamensis, which differs from D. antarctica ecologically as well as morphologically, is indeed a reproductively isolated species. Furthermore, our replicated analyses show that D. chathamensis cannot be reliably distinguished phylogenetically from closely related D. antarctica using subsets (ranging in size from 400 to 10 000 sites) of the 40 912 parsimony-informative SNPs in our data set and that bootstrap values alone can give misleading impressions of the strength of phylogenetic inferences. These results highlight the importance of independently replicating SNP analyses to verify that phylogenetic inferences based on nontargeted SNP data are robust. Our study also demonstrates that modern genomic approaches can be used to identify cases of recent or incipient speciation that traditional approaches (e.g. Sanger sequencing of a few loci) may be unable to detect or resolve.

  9. Dynamics and spatial structure of ENSO from re-analyses versus CMIP5 models

    NASA Astrophysics Data System (ADS)

    Serykh, Ilya; Sonechkin, Dmitry

    2016-04-01

    Basing on a mathematical idea about the so-called strange nonchaotic attractor (SNA) in the quasi-periodically forced dynamical systems, the currently available re-analyses data are considered. It is found that the El Niño - Southern Oscillation (ENSO) is driven not only by the seasonal heating, but also by three more external periodicities (incommensurate to the annual period) associated with the ~18.6-year lunar-solar nutation of the Earth rotation axis, ~11-year sunspot activity cycle and the ~14-month Chandler wobble in the Earth's pole motion. Because of the incommensurability of their periods all four forces affect the system in inappropriate time moments. As a result, the ENSO time series look to be very complex (strange in mathematical terms) but nonchaotic. The power spectra of ENSO indices reveal numerous peaks located at the periods that are multiples of the above periodicities as well as at their sub- and super-harmonic. In spite of the above ENSO complexity, a mutual order seems to be inherent to the ENSO time series and their spectra. This order reveals itself in the existence of a scaling of the power spectrum peaks and respective rhythms in the ENSO dynamics that look like the power spectrum and dynamics of the SNA. It means there are no limits to forecast ENSO, in principle. In practice, it opens a possibility to forecast ENSO for several years ahead. Global spatial structures of anomalies during El Niño and power spectra of ENSO indices from re-analyses are compared with the respective output quantities in the CMIP5 climate models (the Historical experiment). It is found that the models reproduce global spatial structures of the near surface temperature and sea level pressure anomalies during El Niño very similar to these fields in the re-analyses considered. But the power spectra of the ENSO indices from the CMIP5 models show no peaks at the same periods as the re-analyses power spectra. We suppose that it is possible to improve modeled

  10. STRUCTURAL ANALYSES OF FUEL CASKS SUBJECTED TO BOLT PRELOAD, INTERNAL PRESSURE AND SEQUENTIAL DYNAMIC IMPACTS

    SciTech Connect

    Wu, T

    2009-06-25

    Large fuel casks subjected to the combined loads of closure bolt tightening, internal pressure and sequential dynamic impacts present challenges when evaluating their performance in the Hypothetical Accident Conditions (HAC) specified in the Code of Federal Regulations Title 10 Part 71 (10CFR71). Testing is often limited by cost, difficulty in preparing test units and the limited availability of facilities which can carry out such tests. In the past, many casks were evaluated without testing by using simplified analytical methods. In addition, there are no realistic analyses of closure bolt stresses for HAC conditions reported in the open literature. This paper presents a numerical technique for analyzing the accumulated damages of a large fuel cask caused by the sequential loads of the closure bolt tightening and the internal pressure as well as the drop and crash dynamic loads. The bolt preload and the internal pressure are treated as quasi-static loads so that the finite element method with explicit numerical integration scheme based on the theory of wave propagation can be applied. The dynamic impacts with short durations such as the 30-foot drop and the 40-inch puncture for the hypothetical accident conditions specified in 10CFR71 are also analyzed by using the finite-element method with explicit numerical integration scheme.

  11. Combined analytical and numerical approaches in Dynamic Stability analyses of engineering systems

    NASA Astrophysics Data System (ADS)

    Náprstek, Jiří

    2015-03-01

    Dynamic Stability is a widely studied area that has attracted many researchers from various disciplines. Although Dynamic Stability is usually associated with mechanics, theoretical physics or other natural and technical disciplines, it is also relevant to social, economic, and philosophical areas of our lives. Therefore, it is useful to occasionally highlight the general aspects of this amazing area, to present some relevant examples and to evaluate its position among the various branches of Rational Mechanics. From this perspective, the aim of this study is to present a brief review concerning the Dynamic Stability problem, its basic definitions and principles, important phenomena, research motivations and applications in engineering. The relationships with relevant systems that are prone to stability loss (encountered in other areas such as physics, other natural sciences and engineering) are also noted. The theoretical background, which is applicable to many disciplines, is presented. In this paper, the most frequently used Dynamic Stability analysis methods are presented in relation to individual dynamic systems that are widely discussed in various engineering branches. In particular, the Lyapunov function and exponent procedures, Routh-Hurwitz, Liénard, and other theorems are outlined together with demonstrations. The possibilities for analytical and numerical procedures are mentioned together with possible feedback from experimental research and testing. The strengths and shortcomings of these approaches are evaluated together with examples of their effective complementing of each other. The systems that are widely encountered in engineering are presented in the form of mathematical models. The analyses of their Dynamic Stability and post-critical behaviour are also presented. The stability limits, bifurcation points, quasi-periodic response processes and chaotic regimes are discussed. The limit cycle existence and stability are examined together with their

  12. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

    PubMed

    Luo, Yuping; Coskun, Volkan; Liang, Aibing; Yu, Juehua; Cheng, Liming; Ge, Weihong; Shi, Zhanping; Zhang, Kunshan; Li, Chun; Cui, Yaru; Lin, Haijun; Luo, Dandan; Wang, Junbang; Lin, Connie; Dai, Zachary; Zhu, Hongwen; Zhang, Jun; Liu, Jie; Liu, Hailiang; deVellis, Jean; Horvath, Steve; Sun, Yi Eve; Li, Siguang

    2015-05-21

    The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133(+)/GFAP(-) ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133(+)/GFAP(-) quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133(+) ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation.

  13. Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer

    PubMed Central

    Azim, Shafquat; Zubair, Haseeb; Srivastava, Sanjeev K.; Bhardwaj, Arun; Zubair, Asif; Ahmad, Aamir; Singh, Seema; Khushman, Moh’d.; Singh, Ajay P.

    2016-01-01

    We have recently demonstrated that the transcription factor MYB can modulate several cancer-associated phenotypes in pancreatic cancer. In order to understand the molecular basis of these MYB-associated changes, we conducted deep-sequencing of transcriptome of MYB-overexpressing and -silenced pancreatic cancer cells, followed by in silico pathway analysis. We identified significant modulation of 774 genes upon MYB-silencing (p < 0.05) that were assigned to 25 gene networks by in silico analysis. Further analyses placed genes in our RNA sequencing-generated dataset to several canonical signalling pathways, such as cell-cycle control, DNA-damage and -repair responses, p53 and HIF1α. Importantly, we observed downregulation of the pancreatic adenocarcinoma signaling pathway in MYB-silenced pancreatic cancer cells exhibiting suppression of EGFR and NF-κB. Decreased expression of EGFR and RELA was validated by both qPCR and immunoblotting and they were both shown to be under direct transcriptional control of MYB. These observations were further confirmed in a converse approach wherein MYB was overexpressed ectopically in a MYB-null pancreatic cancer cell line. Our findings thus suggest that MYB potentially regulates growth and genomic stability of pancreatic cancer cells via targeting complex gene networks and signaling pathways. Further in-depth functional studies are warranted to fully understand MYB signaling in pancreatic cancer. PMID:27354262

  14. Combination of transcriptomic and metabolomic analyses reveals a JAZ repressor in the jasmonate signaling pathway of Salvia miltiorrhiza

    PubMed Central

    Ge, Qian; Zhang, Yuan; Hua, Wen-Ping; Wu, Yu-Cui; Jin, Xin-Xin; Song, Shuang-Hong; Wang, Zhe-Zhi

    2015-01-01

    Jasmonates (JAs) are plant-specific key signaling molecules that respond to various stimuli and are involved in the synthesis of secondary metabolites. However, little is known about the JA signal pathway, especially in economically significant medicinal plants. To determine the functions of novel genes that participate in the JA-mediated accumulation of secondary metabolites, we examined the metabolomic and transcriptomic signatures from Salvia miltiorrhiza. For the metabolome, 35 representative metabolites showing significant changes in rates of accumulation were extracted and identified. We also screened out 2131 differentially expressed unigenes, of which 30 were involeved in the phenolic secondary metabolic pathway, while 25 were in the JA biosynthesis and signal pathways. Among several MeJA-induced novel genes, SmJAZ8 was selected for detailed functional analysis. Transgenic plants over-expressing SmJAZ8 exhibited a JA-insensitive phenotype, suggesting that the gene is a transcriptional regulator in the JA signal pathway of S. miltiorrhiza. Furthermore, this transgenic tool revealed that JAZ genes have novel function in the constitutive accumulation of secondary metabolites. Based on these findings, we propose that the combined strategy of transcriptomic and metabolomic analyses is valuable for efficient discovery of novel genes in plants. PMID:26388160

  15. Analysing calcium signalling of cells under high shear flows using discontinuous dielectrophoresis

    NASA Astrophysics Data System (ADS)

    Soffe, Rebecca; Baratchi, Sara; Tang, Shi-Yang; Nasabi, Mahyar; McIntyre, Peter; Mitchell, Arnan; Khoshmanesh, Khashayar

    2015-07-01

    Immobilisation of cells is an important feature of many cellular assays, as it enables the physical/chemical stimulation of cells; whilst, monitoring cellular processes using microscopic techniques. Current approaches for immobilising cells, however, are hampered by time-consuming processes, the need for specific antibodies or coatings, and adverse effects on cell integrity. Here, we present a dielectrophoresis-based approach for the robust immobilisation of cells, and analysis of their responses under high shear flows. This approach is quick and label-free, and more importantly, minimises the adverse effects of electric field on the cell integrity, by activating the field for a short duration of 120 s, just long enough to immobilise the cells, after which cell culture media (such as HEPES) is flushed through the platform. In optimal conditions, at least 90% of the cells remained stably immobilised, when exposed to a shear stress of 63 dyn/cm2. This approach was used to examine the shear-induced calcium signalling of HEK-293 cells expressing a mechanosensitive ion channel, transient receptor potential vaniloid type 4 (TRPV4), when exposed to the full physiological range of shear stress.

  16. In silico analyses of dystrophin Dp40 cellular distribution, nuclear export signals and structure modeling.

    PubMed

    Martínez-Herrera, Alejandro; Aragón, Jorge; Bermúdez-Cruz, Rosa Ma; Bazán, Ma Luisa; Soid-Raggi, Gabriela; Ceja, Víctor; Santos Coy-Arechavaleta, Andrea; Alemán, Víctor; Depardón, Francisco; Montañez, Cecilia

    2015-09-01

    Dystrophin Dp40 is the shortest protein encoded by the DMD (Duchenne muscular dystrophy) gene. This protein is unique since it lacks the C-terminal end of dystrophins. In this data article, we describe the subcellular localization, nuclear export signals and the three-dimensional structure modeling of putative Dp40 proteins using bioinformatics tools. The Dp40 wild type protein was predicted as a cytoplasmic protein while the Dp40n4 was predicted to be nuclear. Changes L93P and L170P are involved in the nuclear localization of Dp40n4 protein. A close analysis of Dp40 protein scored that amino acids (93)LEQEHNNLV(101) and (168)LLLHDSIQI(176) could function as NES sequences and the scores are lost in Dp40n4. In addition, the changes L93/170P modify the tertiary structure of putative Dp40 mutants. The analysis showed that changes of residues 93 and 170 from leucine to proline allow the nuclear localization of Dp40 proteins. The data described here are related to the research article entitled "EF-hand domains are involved in the differential cellular distribution of dystrophin Dp40" (J. Aragón et al. Neurosci. Lett. 600 (2015) 115-120) [1].

  17. In silico analyses of dystrophin Dp40 cellular distribution, nuclear export signals and structure modeling

    PubMed Central

    Martínez-Herrera, Alejandro; Aragón, Jorge; Bermúdez-Cruz, Rosa Ma.; Bazán, Ma. Luisa; Soid-Raggi, Gabriela; Ceja, Víctor; Santos Coy-Arechavaleta, Andrea; Alemán, Víctor; Depardón, Francisco; Montañez, Cecilia

    2015-01-01

    Dystrophin Dp40 is the shortest protein encoded by the DMD (Duchenne muscular dystrophy) gene. This protein is unique since it lacks the C-terminal end of dystrophins. In this data article, we describe the subcellular localization, nuclear export signals and the three-dimensional structure modeling of putative Dp40 proteins using bioinformatics tools. The Dp40 wild type protein was predicted as a cytoplasmic protein while the Dp40n4 was predicted to be nuclear. Changes L93P and L170P are involved in the nuclear localization of Dp40n4 protein. A close analysis of Dp40 protein scored that amino acids 93LEQEHNNLV101 and 168LLLHDSIQI176 could function as NES sequences and the scores are lost in Dp40n4. In addition, the changes L93/170P modify the tertiary structure of putative Dp40 mutants. The analysis showed that changes of residues 93 and 170 from leucine to proline allow the nuclear localization of Dp40 proteins. The data described here are related to the research article entitled “EF-hand domains are involved in the differential cellular distribution of dystrophin Dp40” (J. Aragón et al. Neurosci. Lett. 600 (2015) 115–120) [1]. PMID:26217814

  18. Dynamic speckle-interferometer for intracellular processes analyses at high optical magnification

    NASA Astrophysics Data System (ADS)

    Baharev, A. A.; Vladimirov, A. P.; Malygin, A. S.; Mikhailova, Y. A.; Novoselova, I. A.; Yakin, D. I.; Druzhinin, A. V.

    2015-05-01

    At present work dynamic of biospeckles is used for studying processes occurring in cells which arranged in the one layer. The basis of many diseases is changes in the structural and functional properties of the molecular cells components as caused by the influence of external factors and internal functional disorders. Purpose of work is approbation of speckle-interferometer designed for the analysis of cellular metabolism in individual cells. As a parameter, characterizing the metabolic activity of cells used the value of the correlation coefficient (η) of optical signals proportional to the radiation intensity I, recorded at two points in time t. At 320x magnification for the cell diameter of 20 microns value η can be determined in the area size of 6 microns.

  19. Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

    PubMed Central

    Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D.; Elks, Cathy E.; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A.; Franke, Lude L.; Huffman, Jennifer E.; Keller, Margaux F.; McArdle, Patrick F.; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Smith, Jennifer A.; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V.; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arndt, Volker; Arnold, Alice M.; Barbieri, Caterina; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J.; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J.; Chapman, J. Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J.; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eicher, John D.; Fasching, Peter A.; Faul, Jessica D.; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E.; García-Closas, Montserrat; Giles, Graham G.; Girotto, Giorgia G.; Goldberg, Mark S.; González-Neira, Anna; Goodarzi, Mark O.; Grove, Megan L.; Gudbjartsson, Daniel F.; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Henderson, Brian E.; Hocking, Lynne J.; Hofman, Albert; Homuth, Georg; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Huang, Jinyan; Humphreys, Keith; Hunter, David J.; Jakubowska, Anna; Jones, Samuel E.; Kabisch, Maria; Karasik, David; Knight, Julia A.; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian’an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G.; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M.; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B.; Nordestgaard, Børge G.; Olson, Janet E.; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D.P.; Pirastu, Nicola N.; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M.; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J.; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F.; Sanna, Serena; Sawyer, Elinor J.; Schlessinger, David; Schmidt, Marjanka K.; Schmidt, Frank; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Robert A.; Seynaeve, Caroline M.; Simard, Jacques; Sorice, Rossella; Southey, Melissa C.; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D.; Thorsteinsdottir, Unnur; Toland, Amanda E.; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T.; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F.; Winqvist, Robert; Wolffenbuttel, Bruce B.H.R.; Wright, Alan F.; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I.; Buring, Julie E.; Ferrucci, Luigi; Montgomery, Grant W.; Gudnason, Vilmundur; Spector, Tim D.; van Duijn, Cornelia M; Alizadeh, Behrooz Z.; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F.; Gasparini, Paolo P.; Gieger, Christian; Harris, Tamara B.; Hayward, Caroline; Kardia, Sharon L.R.; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C.; Reiner, Alex P.; Ridker, Paul M.; Rotter, Jerome I.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Weir, David R.; Yerges-Armstrong, Laura M.; Price, Alkes L.; Stefansson, Kari; Visser, Jenny A.; Ong, Ken K.; Chang-Claude, Jenny; Murabito, Joanne M.; Perry, John R.B.; Murray, Anna

    2015-01-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage-response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms. PMID:26414677

  20. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

    PubMed

    Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Gonçalo R; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J; Chapman, J Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J; Coviello, Andrea D; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eicher, John D; Fasching, Peter A; Faul, Jessica D; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E; García-Closas, Montserrat; Giles, Graham G; Girotto, Giorgia G; Goldberg, Mark S; González-Neira, Anna; Goodarzi, Mark O; Grove, Megan L; Gudbjartsson, Daniel F; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A; Hall, Per; Hamann, Ute; Henderson, Brian E; Hocking, Lynne J; Hofman, Albert; Homuth, Georg; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Huang, Jinyan; Humphreys, Keith; Hunter, David J; Jakubowska, Anna; Jones, Samuel E; Kabisch, Maria; Karasik, David; Knight, Julia A; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian'an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Benjamin M; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B; Nordestgaard, Børge G; Olson, Janet E; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D P; Pirastu, Nicola N; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F; Sanna, Serena; Sawyer, Elinor J; Schlessinger, David; Schmidt, Marjanka K; Schmidt, Frank; Schmutzler, Rita K; Schoemaker, Minouk J; Scott, Robert A; Seynaeve, Caroline M; Simard, Jacques; Sorice, Rossella; Southey, Melissa C; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D; Thorsteinsdottir, Unnur; Toland, Amanda E; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F; Winqvist, Robert; Wolffenbuttel, Bruce B H R; Wright, Alan F; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I; Buring, Julie E; Ferrucci, Luigi; Montgomery, Grant W; Gudnason, Vilmundur; Spector, Tim D; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F; Gasparini, Paolo P; Gieger, Christian; Harris, Tamara B; Hayward, Caroline; Kardia, Sharon L R; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C; Reiner, Alex P; Ridker, Paul M; Rotter, Jerome I; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Weir, David R; Yerges-Armstrong, Laura M; Price, Alkes L; Stefansson, Kari; Visser, Jenny A; Ong, Ken K; Chang-Claude, Jenny; Murabito, Joanne M; Perry, John R B; Murray, Anna

    2015-11-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

  1. Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation.

    PubMed

    Tan, Haiyan; Yang, Kai; Li, Yuxin; Shaw, Timothy I; Wang, Yanyan; Blanco, Daniel Bastardo; Wang, Xusheng; Cho, Ji-Hoon; Wang, Hong; Rankin, Sherri; Guy, Cliff; Peng, Junmin; Chi, Hongbo

    2017-03-21

    The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulatory networks underlying T cell activation. T cell receptors activated the T cell proteome and phosphoproteome with discrete kinetics, marked by early dynamics of phosphorylation and delayed ribosome biogenesis and mitochondrial activation. Systems biology analyses identified multiple functional modules, active kinases, transcription factors and connectivity between them, and mitochondrial pathways including mitoribosomes and complex IV. Genetic perturbation revealed physiological roles for mitochondrial enzyme COX10-mediated oxidative phosphorylation in T cell quiescence exit. Our multi-layer proteomics profiling, integrative network analysis, and functional studies define landscapes of the T cell proteome and phosphoproteome and reveal signaling and bioenergetics pathways that mediate lymphocyte exit from quiescence.

  2. Structural Dynamic Analyses And Test Predictions For Spacecraft Structures With Non-Linearities

    NASA Astrophysics Data System (ADS)

    Vergniaud, Jean-Baptiste; Soula, Laurent; Newerla, Alfred

    2012-07-01

    The overall objective of the mechanical development and verification process is to ensure that the spacecraft structure is able to sustain the mechanical environments encountered during launch. In general the spacecraft structures are a-priori assumed to behave linear, i.e. the responses to a static load or dynamic excitation, respectively, will increase or decrease proportionally to the amplitude of the load or excitation induced. However, past experiences have shown that various non-linearities might exist in spacecraft structures and the consequences of their dynamic effects can significantly affect the development and verification process. Current processes are mainly adapted to linear spacecraft structure behaviour. No clear rules exist for dealing with major structure non-linearities. They are handled outside the process by individual analysis and margin policy, and analyses after tests to justify the CLA coverage. Non-linearities can primarily affect the current spacecraft development and verification process on two aspects. Prediction of flights loads by launcher/satellite coupled loads analyses (CLA): only linear satellite models are delivered for performing CLA and no well-established rules exist how to properly linearize a model when non- linearities are present. The potential impact of the linearization on the results of the CLA has not yet been properly analyzed. There are thus difficulties to assess that CLA results will cover actual flight levels. Management of satellite verification tests: the CLA results generated with a linear satellite FEM are assumed flight representative. If the internal non- linearities are present in the tested satellite then there might be difficulties to determine which input level must be passed to cover satellite internal loads. The non-linear behaviour can also disturb the shaker control, putting the satellite at risk by potentially imposing too high levels. This paper presents the results of a test campaign performed in

  3. Nonlinear estimation of coherent phase vibrations for statistical signals through multivariable analyses

    NASA Astrophysics Data System (ADS)

    Deng, Linhua

    2015-07-01

    Three nonlinear analysis techniques, including cross-recurrence plot, line of synchronization, and cross-wavelet transform, are proposed to estimate the coherent phase vibrations of nonlinear and non-stationary time series. The case study utilizes the monthly averages of sunspot areas during the time interval from May 1874 to August 2014. The following prominent results are found: (1) the phase-leading hemisphere of long-term sunspot areas has changed twice in the past 140 years, indicating that the hemispheric imbalances and apparent phase differences on both hemispheres are a prevalent behavior and are not anomalous; (2) the alternating regularity of hemispheric asynchronism exhibits a cyclical pattern of 4.5+3.5 cycles, and the magnetic flux excess in a certain hemisphere during the ascending branch of a cycle can be taken as an indication of the phase-leading hemisphere in this cycle. We firmly believe that powerful nonlinear approaches are more advanced than classical linear methods when they are combined to determine the dynamic complexity of nonlinear physical systems.

  4. Three isoparametric solid elements for NASTRAN. [for static, dynamic, buckling, and heat transfer analyses

    NASA Technical Reports Server (NTRS)

    Johnson, S. E.; Field, E. I.

    1973-01-01

    Linear, quadratic, and cubic isoparametric hexahedral solid elements have been added to the element library of NASTRAN. These elements are available for static, dynamic, buckling, and heat-transfer analyses. Because the isoparametric element matrices are generated by direct numerical integration over the volume of the element, variations in material properties, temperatures, and stresses within the elements are represented in the computations. In order to compare the accuracy of the new elements, three similar models of a slender cantilever were developed, one for each element. All elements performed well. As expected, however, the linear element model yielded excellent results only when shear behavior predominated. In contrast, the results obtained from the quadratic and cubic element models were excellent in both shear and bending.

  5. Stream restoration in dynamic fluvial systems: Scientific approaches, analyses, and tools

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2012-04-01

    In the United States the average annual investment in river restoration programs is approximately $1 billion. Despite this burgeoning industry, the National Water Quality Inventory, which tracks the health of the nation's rivers, has shown no serious improvement in cumulative river health since the early 1990s. In the AGU monographStream Restoration in Dynamic Fluvial Systems: Scientific Approaches, Analyses, and Tools, editors Andrew Simon, Sean J. Bennett, and Janine M. Castro pull together the latest evidence-based understanding of stream restoration practices, with an aim of guiding the further development of the field and helping to right its apparently unsuccessful course. In this interview, Eos talks to Sean J. Bennett, University of Buffalo, about the culture, practice, and promise of restoring rivers.

  6. A comprehensive tool to analyse dynamic log files from an Elekta-Synergy accelerator

    NASA Astrophysics Data System (ADS)

    Arumugam, Sankar; Xing, Aitang; Pagulayan, Claire; Holloway, Lois

    2014-03-01

    This study presents the development of a software tool 'Treat Check' to analyse the dynamic log files from an Elekta - Synergy accelerator. The software generates formatted output in the form of a plot presenting errors in various treatment delivery parameters such as gantry angle, Multi Leaf Collimator (MLC) leaf position, jaw position and Monitor Units (MU) for each of the control-points (CP) of the treatment beam. The plots are automatically saved in Portable Document Format (pdf). The software also has the functionality to introduce these treatment delivery errors into the original plan in the Pinnacle (Philips) treatment planning system (TPS) in order to assess the clinical impact of treatment delivery errors on delivered dose.

  7. Analyses of the dynamic docking test system for advanced mission docking system test programs. [Apollo Soyuz Test Project

    NASA Technical Reports Server (NTRS)

    Gates, R. M.; Williams, J. E.

    1974-01-01

    Results are given of analytical studies performed in support of the design, implementation, checkout and use of NASA's dynamic docking test system (DDTS). Included are analyses of simulator components, a list of detailed operational test procedures, a summary of simulator performance, and an analysis and comparison of docking dynamics and loads obtained by test and analysis.

  8. A Dynamic Stimulus-Driven Model of Signal Detection

    ERIC Educational Resources Information Center

    Turner, Brandon M.; Van Zandt, Trisha; Brown, Scott

    2011-01-01

    Signal detection theory forms the core of many current models of cognition, including memory, choice, and categorization. However, the classic signal detection model presumes the a priori existence of fixed stimulus representations--usually Gaussian distributions--even when the observer has no experience with the task. Furthermore, the classic…

  9. Modeling Oncogenic Signaling in Colon Tumors by Multidirectional Analyses of Microarray Data Directed for Maximization of Analytical Reliability

    PubMed Central

    Rubel, Tymon; Paziewska, Agnieszka; Mikula, Michal; Jarosz, Dorota; Pachlewski, Jacek; Oledzki, Janusz; Ostrowsk, Jerzy

    2010-01-01

    Background Clinical progression of colorectal cancers (CRC) may occur in parallel with distinctive signaling alterations. We designed multidirectional analyses integrating microarray-based data with biostatistics and bioinformatics to elucidate the signaling and metabolic alterations underlying CRC development in the adenoma-carcinoma sequence. Methodology/Principal Findings Studies were performed on normal mucosa, adenoma, and carcinoma samples obtained during surgery or colonoscopy. Collections of cryostat sections prepared from the tissue samples were evaluated by a pathologist to control the relative cell type content. The measurements were done using Affymetrix GeneChip HG-U133plus2, and probe set data was generated using two normalization algorithms: MAS5.0 and GCRMA with least-variant set (LVS). The data was evaluated using pair-wise comparisons and data decomposition into singular value decomposition (SVD) modes. The method selected for the functional analysis used the Kolmogorov-Smirnov test. Expressional profiles obtained in 105 samples of whole tissue sections were used to establish oncogenic signaling alterations in progression of CRC, while those representing 40 microdissected specimens were used to select differences in KEGG pathways between epithelium and mucosa. Based on a consensus of the results obtained by two normalization algorithms, and two probe set sorting criteria, we identified 14 and 17 KEGG signaling and metabolic pathways that are significantly altered between normal and tumor samples and between benign and malignant tumors, respectively. Several of them were also selected from the raw microarray data of 2 recently published studies (GSE4183 and GSE8671). Conclusion/Significance Although the proposed strategy is computationally complex and labor–intensive, it may reduce the number of false results. PMID:20957034

  10. Deconvolution analyses with tent functions reveal delayed and long-sustained increases of BOLD signals with acupuncture stimulation.

    PubMed

    Murase, Tomokazu; Umeda, Masahiro; Fukunaga, Masaki; Tanaka, Chuzo; Higuchi, Toshihiro

    2013-01-01

    We used deconvolution analysis to examine temporal changes in brain activity after acupuncture stimulation and assess brain responses without expected reference functions. We also examined temporal changes in brain activity after sham acupuncture (noninsertive) and scrubbing stimulation. We divided 26 healthy right-handed adults into a group of 13 who received real acupuncture with manual manipulation and a group of 13 who received both tactical stimulations. Functional magnetic resonance imaging (fMRI) sequences consisted of four 15-s stimulation blocks (ON) interspersed between one 30-s and four 45-s rest blocks (OFF) for a total scanning time of 270 s. We analyzed data by using Statistical Parametric Mapping 8 (SPM8), MarsBaR, and Analysis of Functional NeuroImages (AFNI) software. For statistical analysis, we used 3dDeconvolve, part of the AFNI package, to extract the impulse response functions (IRFs) of the fMRI signals on a voxel-wise basis, and we tested the time courses of the extracted IRFs for the stimulations. We found stimulus-specific impulse responses of blood oxygen level-dependent (BOLD) signals in various brain regions. We observed significantly delayed and long-sustained increases of BOLD signals in several brain regions following real acupuncture compared to sham acupuncture and palm scrubbing, which we attribute to peripheral nocireceptors, flare responses, and processing of the central nervous system. Acupuncture stimulation induced continued activity that was stronger than activity after the other stimulations. We used tent function deconvolution to process fMRI data for acupuncture stimulation and found delayed increasing and delayed decreasing changes in BOLD signal in the somatosensory areas and areas related to pain perception. Deconvolution analyses with tent functions are expected to be useful in extracting complicated and associated brain activity that is delayed and sustained for a long period after various stimulations.

  11. Field Crickets Compensate for Unattractive Static Long-Distance Call Components by Increasing Dynamic Signalling Effort.

    PubMed

    McAuley, Emily M; Bertram, Susan M

    2016-01-01

    The evolution of multiple sexual signals presents a dilemma since individuals selecting a mate should pay attention to the most honest signal and ignore the rest; however, multiple signals may evolve if, together, they provide more information to the receiver than either one would alone. Static and dynamic signals, for instance, can act as multiple messages, providing information on different aspects of signaller quality that reflect condition at different time scales. While the nature of static signals makes them difficult or impossible for individuals to augment, dynamic signals are much more susceptible to temporary fluctuations in effort. We investigated whether male Texas field crickets, Gryllus texensis, that produce unattractive static signals compensate by dynamically increasing their calling effort. Our findings lend partial support to the compensation hypothesis, as males that called at unattractive carrier frequencies (a static trait) spent more time calling each night (a dynamic trait). Interestingly, this finding was most pronounced in males that called with attractive pulse characteristics (static traits) but did not occur in males that called with unattractive pulse characteristics. Males that signalled with unattractive pulse characteristics (duration and pause) spent less time calling through the night. Our correlative findings on wild caught males suggest that only males that signal with attractive pulse characteristics may be able to afford to pay the costs of both trait exaggeration and increased calling effort to compensate for poor carrier frequencies.

  12. Field Crickets Compensate for Unattractive Static Long-Distance Call Components by Increasing Dynamic Signalling Effort

    PubMed Central

    McAuley, Emily M.

    2016-01-01

    The evolution of multiple sexual signals presents a dilemma since individuals selecting a mate should pay attention to the most honest signal and ignore the rest; however, multiple signals may evolve if, together, they provide more information to the receiver than either one would alone. Static and dynamic signals, for instance, can act as multiple messages, providing information on different aspects of signaller quality that reflect condition at different time scales. While the nature of static signals makes them difficult or impossible for individuals to augment, dynamic signals are much more susceptible to temporary fluctuations in effort. We investigated whether male Texas field crickets, Gryllus texensis, that produce unattractive static signals compensate by dynamically increasing their calling effort. Our findings lend partial support to the compensation hypothesis, as males that called at unattractive carrier frequencies (a static trait) spent more time calling each night (a dynamic trait). Interestingly, this finding was most pronounced in males that called with attractive pulse characteristics (static traits) but did not occur in males that called with unattractive pulse characteristics. Males that signalled with unattractive pulse characteristics (duration and pause) spent less time calling through the night. Our correlative findings on wild caught males suggest that only males that signal with attractive pulse characteristics may be able to afford to pay the costs of both trait exaggeration and increased calling effort to compensate for poor carrier frequencies. PMID:27936045

  13. Parameter space exploration within dynamic simulations of signaling networks.

    PubMed

    De Ambrosi, Cristina; Barla, Annalisa; Tortolina, Lorenzo; Castagnino, Nicoletta; Pesenti, Raffaele; Verri, Alessandro; Ballestrero, Alberto; Patrone, Franco; Parodi, Silvio

    2013-02-01

    We started offering an introduction to very basic aspects of molecular biology, for the reader coming from computer sciences, information technology, mathematics. Similarly we offered a minimum of information about pathways and networks in graph theory, for a reader coming from the bio-medical sector. At the crossover about the two different types of expertise, we offered some definition about Systems Biology. The core of the article deals with a Molecular Interaction Map (MIM), a network of biochemical interactions involved in a small signaling-network sub-region relevant in breast cancer. We explored robustness/sensitivity to random perturbations. It turns out that our MIM is a non-isomorphic directed graph. For non physiological directions of propagation of the signal the network is quite resistant to perturbations. The opposite happens for biologically significant directions of signal propagation. In these cases we can have no signal attenuation, and even signal amplification. Signal propagation along a given pathway is highly unidirectional, with the exception of signal-feedbacks, that again have a specific biological role and significance. In conclusion, even a relatively small network like our present MIM reveals the preponderance of specific biological functions over unspecific isomorphic behaviors. This is perhaps the consequence of hundreds of millions of years of biological evolution.

  14. Dynamics of BMP signaling in limb bud mesenchyme and polydactyly.

    PubMed

    Norrie, Jacqueline L; Lewandowski, Jordan P; Bouldin, Cortney M; Amarnath, Smita; Li, Qiang; Vokes, Martha S; Ehrlich, Lauren I R; Harfe, Brian D; Vokes, Steven A

    2014-09-15

    Mutations in the Bone Morphogenetic Protein (BMP) pathway are associated with a range of defects in skeletal formation. Genetic analysis of BMP signaling requirements is complicated by the presence of three partially redundant BMPs that are required for multiple stages of limb development. We generated an inducible allele of a BMP inhibitor, Gremlin, which reduces BMP signaling. We show that BMPs act in a dose and time dependent manner in which early reduction of BMPs result in digit loss, while inhibiting overall BMP signaling between E10.5 and E11.5 allows polydactylous digit formation. During this period, inhibiting BMPs extends the duration of FGF signaling. Sox9 is initially expressed in normal digit ray domains but at reduced levels that correlate with the reduction in BMP signaling. The persistence of elevated FGF signaling likely promotes cell proliferation and survival, inhibiting the activation of Sox9 and secondarily, inhibiting the differentiation of Sox9-expressing chondrocytes. Our results provide new insights into the timing and clarify the mechanisms underlying BMP signaling during digit morphogenesis.

  15. Multi-Platform Metabolomic Analyses of Ergosterol-Induced Dynamic Changes in Nicotiana tabacum Cells

    PubMed Central

    Tugizimana, Fidele; Steenkamp, Paul A.; Piater, Lizelle A.; Dubery, Ian A.

    2014-01-01

    Metabolomics is providing new dimensions into understanding the intracellular adaptive responses in plants to external stimuli. In this study, a multi-technology-metabolomic approach was used to investigate the effect of the fungal sterol, ergosterol, on the metabolome of cultured tobacco cells. Cell suspensions were treated with different concentrations (0–1000 nM) of ergosterol and incubated for different time periods (0–24 h). Intracellular metabolites were extracted with two methods: a selective dispersive liquid-liquid micro-extraction and a general methanol extraction. Chromatographic techniques (GC-FID, GC-MS, GC×GC-TOF-MS, UHPLC-MS) and 1H NMR spectroscopy were used for quantitative and qualitative analyses. Multivariate data analyses (PCA and OPLS-DA models) were used to extract interpretable information from the multidimensional data generated from the analytical techniques. The results showed that ergosterol triggered differential changes in the metabolome of the cells, leading to variation in the biosynthesis of secondary metabolites. PCA scores plots revealed dose- and time-dependent metabolic variations, with optimal treatment conditions being found to be 300 nM ergosterol and an 18 h incubation period. The observed ergosterol-induced metabolic changes were correlated with changes in defence-related metabolites. The ‘defensome’ involved increases in terpenoid metabolites with five antimicrobial compounds (the bicyclic sesquiterpenoid phytoalexins: phytuberin, solavetivone, capsidiol, lubimin and rishitin) and other metabolites (abscisic acid and phytosterols) putatively identified. In addition, various phenylpropanoid precursors, cinnamic acid derivatives and - conjugates, coumarins and lignin monomers were annotated. These annotated metabolites revealed a dynamic reprogramming of metabolic networks that are functionally correlated, with a high complexity in their regulation. PMID:24498209

  16. A system of recurrent neural networks for modularising, parameterising and dynamic analysis of cell signalling networks.

    PubMed

    Samarasinghe, S; Ling, H

    2017-02-04

    In this paper, we show how to extend our previously proposed novel continuous time Recurrent Neural Networks (RNN) approach that retains the advantage of continuous dynamics offered by Ordinary Differential Equations (ODE) while enabling parameter estimation through adaptation, to larger signalling networks using a modular approach. Specifically, the signalling network is decomposed into several sub-models based on important temporal events in the network. Each sub-model is represented by the proposed RNN and trained using data generated from the corresponding ODE model. Trained sub-models are assembled into a whole system RNN which is then subjected to systems dynamics and sensitivity analyses. The concept is illustrated by application to G1/S transition in cell cycle using Iwamoto et al. (2008) ODE model. We decomposed the G1/S network into 3 sub-models: (i) E2F transcription factor release; (ii) E2F and CycE positive feedback loop for elevating cyclin levels; and (iii) E2F and CycA negative feedback to degrade E2F. The trained sub-models accurately represented system dynamics and parameters were in good agreement with the ODE model. The whole system RNN however revealed couple of parameters contributing to compounding errors due to feedback and required refinement to sub-model 2. These related to the reversible reaction between CycE/CDK2 and p27, its inhibitor. The revised whole system RNN model very accurately matched dynamics of the ODE system. Local sensitivity analysis of the whole system model further revealed the most dominant influence of the above two parameters in perturbing G1/S transition, giving support to a recent hypothesis that the release of inhibitor p27 from Cyc/CDK complex triggers cell cycle stage transition. To make the model useful in a practical setting, we modified each RNN sub-model with a time relay switch to facilitate larger interval input data (≈20min) (original model used data for 30s or less) and retrained them that produced

  17. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation

    DTIC Science & Technology

    2012-07-01

    Cluster #1 Fig. 2) contained signaling proteins associated with the Warburg effect (AKT/mTOR/PI3K), insulin -signaling (pACC/IRS1), and epitheilial to...dysregulation of AKT-phosphorylation and resistance to AKT-inhibitors. Nanobiosensor output will be quantitated and validated relative to...within 1 hr of removal from a woman . Fig. 6 illustrates the insertion of the caspase-9 nanoprobe in live RPFNA cytology from high-risk women. Task

  18. Analysing the temporal water quality dynamics of Lake Basaka, Central Rift Valley of Ethiopia

    NASA Astrophysics Data System (ADS)

    Olumana Dinka, Megersa

    2017-01-01

    This study presents the general water quality status and temporal quality dynamics of Lake Basaka water in the past about 5 decades. Water samples were collected and analysed for important physico-chemical quality parameters following standard procedures. The result showed that Lake Basaka water is highly saline and alkaline and experiencing a general reducing trends in ionic concentrations of quality parameters due to the dilution effect. About 10-fold reduction of total ionic concentration occurred in the Lake over the period of 2 decades (1960-1980). There was a sharp and fast decline in EC, Cl, SO4, Na, and K ions from early 1960s up to the late 1980s, and then became relatively stable. Some ions (eg. Na, Ca, Mg, Cl, SO4) are showing increment in recent years. This characteristics of the lake water is terrible in relation to its potential to inundate the nearby areas in the near future. The expansion of such quality water has negative effects on the water resources of the region, especially soil quality, drainage and groundwater, in terms of salinity, sodicity and specific ion toxicity. The regimes of soil moisture, solute and groundwater could be affected, concurrently affecting the productivity and sustainability of the sugar estate. Thus, there is an urgent need to identify the potential sources of water and chemicals to the lake and devise an appropriate mitigation and/or remedial measures.

  19. Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses

    PubMed Central

    Zaade, Daniela; Schmitz, Jennifer; Benke, Eileen; Klare, Sabrina; Seidel, Kerstin; Kirsch, Sebastian; Goldin-Lang, Petra; Zollmann, Frank S.; Unger, Thomas; Funke-Kaiser, Heiko

    2013-01-01

    The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)RR. Furthermore, recent publications suggest that major functions of the (P)RR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATPases. The transcriptome and recruitmentome downstream of the V-ATPase function and PLZF in the context of the (P)RR are currently unknown. Therefore, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (P)RR, stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR. We were able to identify distinct and overlapping genetic signatures as well as novel real-time PCR-validated target genes of the different molecular functions of the (P)RR. Moreover, bioinformatic analyses of our data confirm the role of (P)RŔs signal transduction pathways in cardiovascular disease and tumorigenesis. PMID:23469216

  20. Synthetic antigens reveal dynamics of BCR endocytosis during inhibitory signaling.

    PubMed

    Courtney, Adam H; Bennett, Nitasha R; Zwick, Daniel B; Hudon, Jonathan; Kiessling, Laura L

    2014-01-17

    B cells detect foreign antigens through their B cell antigen receptor (BCR). The BCR, when engaged by antigen, initiates a signaling cascade. Concurrent with signaling is endocytosis of the BCR complex, which acts to downregulate signaling and facilitate uptake of antigen for processing and display on the cell surface. The relationship between signaling and BCR endocytosis is poorly defined. Here, we explore the interplay between BCR endocytosis and antigens that either promote or inhibit B cell activation. Specifically, synthetic antigens were generated that engage the BCR alone or both the BCR and the inhibitory co-receptor CD22. The lectin CD22, a member of the Siglec family, binds sialic acid-containing glycoconjugates found on host tissues, inhibiting BCR signaling to prevent erroneous B cell activation. At low concentrations, antigens that can cocluster the BCR and CD22 promote rapid BCR endocytosis; whereas, slower endocytosis occurs with antigens that bind only the BCR. At higher antigen concentrations, rapid BCR endocytosis occurs upon treatment with either stimulatory or inhibitory antigens. Endocytosis of the BCR, in response to synthetic antigens, results in its entry into early endocytic compartments. Although the CD22-binding antigens fail to activate key regulators of antigen presentation (e.g., Syk), they also promote BCR endocytosis, indicating that inhibitory antigens can be internalized. Together, our observations support a functional role for BCR endocytosis in downregulating BCR signaling. The reduction of cell surface BCR levels in the absence of B cell activation should raise the threshold for BCR subsequent activation. The ability of the activating synthetic antigens to trigger both signaling and entry of the BCR into early endosomes suggests strategies for targeted antigen delivery.

  1. Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway

    PubMed Central

    Čokić, Vladan P.; Mossuz, Pascal; Han, Jing; Socoro, Nuria; Beleslin-Čokić, Bojana B.; Mitrović, Olivera; Subotički, Tijana; Diklić, Miloš; Leković, Danijela; Gotić, Mirjana; Puri, Raj K.; Noguchi, Constance Tom; Schechter, Alan N.

    2015-01-01

    The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34+ cells and granulocytes obtained from peripheral blood of subjects with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). The microarray analyses of the CD34+ cells and granulocytes were performed from 20 de novo MPN subjects: JAK2 positive ET, PV, PMF subjects, and JAK2 negative ET/PMF subjects. The granulocytes for proteomic studies were pooled in 4 groups: PV with JAK2 mutant allele burden above 80%, ET with JAK2 mutation, PMF with JAK2 mutation and ET/PMF with no JAK2 mutation. The number of differentially regulated genes was about two fold larger in CD34+ cells compared to granulocytes. Thirty-six genes (including RUNX1, TNFRSF19) were persistently highly expressed, while 42 genes (including FOXD4, PDE4A) were underexpressed both in CD34+ cells and granulocytes. Using proteomic studies, significant up-regulation was observed for MAPK and PI3K/AKT signaling regulators that control myeloid cell apoptosis and proliferation: RAC2, MNDA, S100A8/9, CORO1A, and GNAI2. When the status of the mTOR signaling pathway related genes was analyzed, PI3K/AKT regulators were preferentially up-regulated in CD34+ cells of MPNs, with down-regulated major components of the protein complex EIF4F. Molecular profiling of CD34+ cells and granulocytes of MPN determined gene expression patterns beyond their recognized function in disease pathogenesis that included dominant up-regulation of PI3K/AKT signaling. PMID:26275051

  2. Comparative proteome analyses reveal that nitric oxide is an important signal molecule in the response of rice to aluminum toxicity.

    PubMed

    Yang, Liming; Tian, Dagang; Todd, Christopher D; Luo, Yuming; Hu, Xiangyang

    2013-03-01

    Acidic soils inhibit crop yield and reduce grain quality. One of the major contributing factors to acidic soil is the presence of soluble aluminum (Al(3+)) ions, but the mechanisms underlying plant responses to Al(3+) toxicity remain elusive. Nitric oxide (NO) is an important messenger and participates in various plant physiological responses. Here, we demonstrate that Al(3+) induced an increase of NO in rice seedlings; adding exogenous NO alleviated the Al(3+) toxicity related to rice growth and photosynthetic capacity, effects that could be reversed by suppressing NO metabolism. Comparative proteomic analyses successfully identified 92 proteins that showed differential expression after Al(3+) or NO treatment. In particular, some of the proteins are involved in reactive oxygen species (ROS) and reactive nitrogen species (RNS) metabolism. Further analyses confirmed that NO treatment reduced Al(3+)-induced ROS and RNS toxicities by increasing the activities and protein expression of antioxidant enzymes, as well as S-nitrosoglutathione reductase (GSNOR). Suppressing GSNOR enzymatic activity aggravated Al(3+) damage to rice and increased the accumulation of RNS. NO treatment altered the expression of proteins associated with cell wall synthesis, cell division and cell structure, calcium signaling and defense responses. On the basis of these results, we propose that NO activates multiple pathways that enhance rice adaptation to Al(3+) toxicity. Such findings may be applicable to crop engineering to enhance yield and improve stress tolerance.

  3. Analyses of the soil surface dynamic of South African Kalahari salt pans based on hyperspectral and multitemporal data

    NASA Astrophysics Data System (ADS)

    Milewski, Robert; Chabrillat, Sabine; Behling, Robert; Mielke, Christian; Schleicher, Anja Maria; Guanter, Luis

    2016-04-01

    The consequences of climate change represent a major threat to sustainable development and growth in Southern Africa. Understanding the impact on the geo- and biosphere is therefore of great importance in this particular region. In this context the Kalahari salt pans (also known as playas or sabkhas) and their peripheral saline and alkaline habitats are an ecosystem of major interest. They are very sensitive to environmental conditions, and as thus hydrological, mineralogical and ecological responses to climatic variations can be analysed. Up to now the soil composition of salt pans in this area have been only assessed mono-temporally and on a coarse regional scale. Furthermore, the dynamic of the salt pans, especially the formation of evaporites, is still uncertain and poorly understood. High spectral resolution remote sensing can estimate evaporite content and mineralogy of soils based on the analyses of the surface reflectance properties within the Visible-Near InfraRed (VNIR 400-1000 nm) and Short-Wave InfraRed (SWIR 1000-2500 nm) regions. In these wavelength regions major chemical components of the soil interact with the electromagnetic radiation and produce characteristic absorption features that can be used to derive the properties of interest. Although such techniques are well established for the laboratory and field scale, the potential of current (Hyperion) and upcoming spaceborne sensors such as EnMAP for quantitative mineralogical and salt spectral mapping is still to be demonstrated. Combined with hyperspectral methods, multitemporal remote sensing techniques allow us to derive the recent dynamic of these salt pans and link the mineralogical analysis of the pan surface to major physical processes in these dryland environments. In this study we focus on the analyses of the Namibian Omongwa salt pans based on satellite hyperspectral imagery and multispectral time-series data. First, a change detection analysis is applied using the Iterative

  4. Dopamine D1 signaling organizes network dynamics underlying working memory

    PubMed Central

    Roffman, Joshua L.; Tanner, Alexandra S.; Eryilmaz, Hamdi; Rodriguez-Thompson, Anais; Silverstein, Noah J.; Ho, New Fei; Nitenson, Adam Z.; Chonde, Daniel B.; Greve, Douglas N.; Abi-Dargham, Anissa; Buckner, Randy L.; Manoach, Dara S.; Rosen, Bruce R.; Hooker, Jacob M.; Catana, Ciprian

    2016-01-01

    Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory–emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits. PMID:27386561

  5. Dynamic Hedgehog signalling pathway activity in germline stem cells.

    PubMed

    Sahin, Z; Szczepny, A; McLaughlin, E A; Meistrich, M L; Zhou, W; Ustunel, I; Loveland, K L

    2014-03-01

    Although the contribution of Hedgehog (Hh) signalling to stem cell development and oncogenesis is well recognised, its importance for spermatogonial stem cells (SSCs) has not been established. Here we interrogate adult rat SSCs using an established model in which only undifferentiated spermatogonial cells remain in the testis at 15 weeks following irradiation, and spermatogonial differentiation is induced within 4 weeks by gonadotrophin-releasing hormone antagonist (GnRH-ant) administration. Synthesis of Hh pathway components in untreated adult rat testes was compared with that in irradiated testes prior to and after GnRH-ant exposure using in situ hybridization. In adult testes with complete spermatogenesis, the Desert Hedgehog ligand transcript, Dhh, was detected in Sertoli cells, some spermatogonia and in spermatocytes by in situ hybridization. Spermatogenic cells were identified as sites of Hh signalling through detection of transcripts encoding the Hh receptor, Ptc2 transcripts and proteins for the key downstream target of Hh signalling, Gli1 and the Hh transcriptional activator, Gli2. Remarkably, the undifferentiated spermatogonia present in irradiated adult rat testes contained Dhh in addition to Ptc2, Gli1 and Gli2, revealing the potential for an autocrine Hh signalling loop to sustain undifferentiated spermatogonial cells. These transcripts became undetectable by in situ hybridization following GnRH-ant induction of spermatogonial differentiation, however, detection of Gli1 protein in spermatogonia in all groups indicates that Hh signalling is sustained. This is the first evidence of active Hh signalling in mammalian male germline stem cells, as has been documented for some cancer stem cells.

  6. Sparse approximation of long-term biomedical signals for classification via dynamic PCA.

    PubMed

    Xie, Shengkun; Jin, Feng; Krishnan, Sridhar

    2011-01-01

    Sparse approximation is a novel technique in applications of event detection problems to long-term complex biomedical signals. It involves simplifying the extent of resources required to describe a large set of data sufficiently for classification. In this paper, we propose a multivariate statistical approach using dynamic principal component analysis along with the non-overlapping moving window technique to extract feature information from univariate long-term observational signals. Within the dynamic PCA framework, a few principal components plus the energy measure of signals in principal component subspace are highly promising for applying event detection problems to both stationary and non-stationary signals. The proposed method has been first tested using synthetic databases which contain various representative signals. The effectiveness of the method is then verified with real EEG signals for the purpose of epilepsy diagnosis and epileptic seizure detection. This sparse method produces a 100% classification accuracy for both synthetic data and real single channel EEG data.

  7. Beyond static biomarkers--The dynamic response potential of signaling networks as an alternate biomarker?

    PubMed

    Kim, Jaeyeon; Schoeberl, Birgit

    2015-12-22

    In this week's issue of Science Signaling, Fey et al. introduce a new type of biomarker. Using the example of neuroblastoma, the authors demonstrate that patient-specific differences in the computed property (the Hill coefficient) of the dynamics of a pathway involved in cell death signaling outperformed the prognostic capability of any single static biomarker alone or in combination.

  8. Ligand-binding dynamics rewire cellular signaling via Estrogen Receptor-α

    PubMed Central

    Srinivasan, Sathish; Nwachukwu, Jerome C.; Parent, Alex A.; Cavett, Valerie; Nowak, Jason; Hughes, Travis S.; Kojetin, Douglas J.; Katzenellenbogen, John A.; Nettles, Kendall W.

    2013-01-01

    Ligand-binding dynamics control allosteric signaling through the estrogen receptor-α (ERα), but the biological consequences of such dynamic binding orientations are unknown. Here, we compare a set of ER ligands having dynamic binding orientation (dynamic ligands) with a control set of isomers that are constrained to bind in a single orientation (constrained ligands). Proliferation of breast cancer cells directed by constrained ligands is associated with DNA binding, coactivator recruitment and activation of the estrogen-induced gene GREB1, reflecting a highly interconnected signaling network. In contrast, proliferation driven by dynamic ligands is associated with induction of ERα-mediated transcription in a DNA-binding domain (DBD)-dependent manner. Further, dynamic ligands displayed enhanced anti-inflammatory activity. The DBD-dependent profile was predictive of these signaling patterns in a larger diverse set of natural and synthetic ligands. Thus, ligand dynamics directs unique signaling pathways, and reveals a novel role of the DBD in allosteric control of ERα-mediated signaling. PMID:23524984

  9. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation

    DTIC Science & Technology

    2011-07-01

    develop nanoprobes capable of sensing biotargets and molecular signaling processes within single living cells, thus providing the important information...for biomedical research and clinical applications. Fiber-optic nanosensors are suitable for sensing intracellular/intercellular physiological and...100-nm spatial resolution (12, 13). Single- molecule detection and imaging schemes using nanofibers could open new capabilities in the investigation of

  10. Signal quality of the LHC AC dipoles and its impact on beam dynamics

    SciTech Connect

    Miyamoto, R.; Cattin, M.; Serrano, J.; Tomas, R.

    2010-05-23

    The adiabaticity of the AC dipole might be compromised by noise or unwanted frequency components in its signal. An effort has been put to characterize and optimize the signal quality of the LHC AC dipoles. The measured signal is used in realistic simulations in order to evaluate its impact on beam dynamics and to ultimately establish safe margins for the operation of the LHC AC dipoles.

  11. Investigating carbon dynamics in Siberian peat bogs using molecular-level analyses

    NASA Astrophysics Data System (ADS)

    Kaiser, K.; Benner, R. H.

    2013-12-01

    Total hydrolysable carbohydrates, and lignin and cutin acid compounds were analyzed in peat cores collected 56.8 N (SIB04), 58.4 N (SIB06), 63.8 N (G137) and 66.5 N (E113) in the Western Siberian Lowland to investigate vegetation, chemical compositions and the stage of decomposition. Sphagnum mosses dominated peatland vegetation in all four cores. High-resolution molecular analyses revealed rapid vegetation changes on timescales of 50-200 years in the southern cores Sib4 and Sib6. Syringyl and vanillyl (S/V) ratios and cutin acids indicated these vegetation changes were due to varying inputs of angiosperm and gymnosperm and root material. In the G137 and E113 cores lichens briefly replaced sphagnum mosses and vascular plants. Molecular decomposition indicators used in this study tracked the decomposition of different organic constituents of peat organic matter. The carbohydrate decomposition index was sensitive to the polysaccharide component of all peat-forming plants, whereas acid/aldehyde ratios of S and V phenols (Ac/AlS,V) followed the lignin component of vascular plants. Low carbohydrate decomposition indices in peat layers corresponded well with elevated (Ad/Al)S,V ratios. This suggested both classes of biochemicals were simultaneously decomposed, and decomposition processes were associated with extensive total mass loss in these ombrotrophic systems. Selective decomposition or transformation of lignin was observed in the permafrost-influenced northern cores G137 and E113. Both cores exhibited the highest (Ad/Al)S,V ratios, almost four-fold higher than measured in peat-forming plants. The extent of decomposition in the four peat cores did not uniformly increase with age, but showed episodic extensive decomposition events. Variable decomposition events independent of climatic conditions and vegetation shifts highlight the complexity of peatland dynamics.

  12. Who Is Overeducated and Why? Probit and Dynamic Mixed Multinomial Logit Analyses of Vertical Mismatch in East and West Germany

    ERIC Educational Resources Information Center

    Boll, Christina; Leppin, Julian Sebastian; Schömann, Klaus

    2016-01-01

    Overeducation potentially signals a productivity loss. With Socio-Economic Panel data from 1984 to 2011 we identify drivers of educational mismatch for East and West medium and highly educated Germans. Addressing measurement error, state dependence and unobserved heterogeneity, we run dynamic mixed multinomial logit models for three different…

  13. The impacts of hypnotic susceptibility on chaotic dynamics of EEG signals during standard tasks of Waterloo-Stanford Group Scale.

    PubMed

    Yargholi, Elahe'; Nasrabadi, Ali Motie

    2013-05-01

    Chaotic features of hypnotic EEG (electroencephalograph), recorded during standard tasks of Waterloo-Stanford Group Scale of hypnotic susceptibility (WSGS), were used to investigate the underlying dynamic of tasks and analyse the effect of hypnotic depth and concentration on EEG signals. Results demonstrate: (1) More efficiency of Higuchi dimension in comparison with Correlation dimension to distinguish subjects from different hypnotizable groups, (2) Channels with significantly different chaotic features among people from various hypnotizability levels in tasks, (3) High level of consistency among discriminating channels of tasks with function of brain's lobes, (4) Most affectability of medium hypnotizable subjects and (5) Rise in fractal dimensions due to increase in hypnosis depth.

  14. Spectral signals from electronic dynamics in sodium clusters

    SciTech Connect

    Calvayrac, F.; Reinhard, P.G.; Suraud, E.

    1997-03-01

    We study the dynamics of the electron cloud in sodium clusters for small and large amplitude excitations in the time-dependent local-density approximation (TDLDA), without referring to linear approximations. In particular, we discuss the interpretation of strength function and power spectrum as obtained from dynamical calculations. We demonstrate the constructive and destructive interference contained in the various spectral states. We search for a special signature of nonlinear couplings in the large amplitude regime, but do not find pronounced effects. {copyright} 1997 Academic Press, Inc.

  15. Integration of Predictive Routing Information with Dynamic Traffic Signal Control

    DTIC Science & Technology

    1994-05-01

    vehicles without the on-board guidance aid (Harris, S., Rabone , A., et.al., 1992). The simulation developed was called ROute GUidance Simulation (ROGUS...Florida. Harris, S., Rabone , A., et.al. 1992. ROGUS: A Simulation of Dynamic Route Guidance Systems. Traffic Engineering and Control(33)327-329

  16. Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons

    PubMed Central

    Kruse, Martin; Vivas, Oscar; Traynor-Kaplan, Alexis

    2016-01-01

    In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P2 levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca2+ upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P2 in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P2-dependent processes in neurons. SIGNIFICANCE STATEMENT Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2 via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2 is essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We studied the dynamics of phosphoinositide metabolism in sympathetic neurons upon muscarinic stimulation and used the kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show a several-fold faster synthesis of PI(4,5)P2 in sympathetic neurons than in an electrically nonexcitable cell line, and provide a framework for future studies of PI(4,5)P2-dependent processes in neurons. PMID:26818524

  17. Dynamic facial expressions of emotion transmit an evolving hierarchy of signals over time.

    PubMed

    Jack, Rachael E; Garrod, Oliver G B; Schyns, Philippe G

    2014-01-20

    Designed by biological and social evolutionary pressures, facial expressions of emotion comprise specific facial movements to support a near-optimal system of signaling and decoding. Although highly dynamical, little is known about the form and function of facial expression temporal dynamics. Do facial expressions transmit diagnostic signals simultaneously to optimize categorization of the six classic emotions, or sequentially to support a more complex communication system of successive categorizations over time? Our data support the latter. Using a combination of perceptual expectation modeling, information theory, and Bayesian classifiers, we show that dynamic facial expressions of emotion transmit an evolving hierarchy of "biologically basic to socially specific" information over time. Early in the signaling dynamics, facial expressions systematically transmit few, biologically rooted face signals supporting the categorization of fewer elementary categories (e.g., approach/avoidance). Later transmissions comprise more complex signals that support categorization of a larger number of socially specific categories (i.e., the six classic emotions). Here, we show that dynamic facial expressions of emotion provide a sophisticated signaling system, questioning the widely accepted notion that emotion communication is comprised of six basic (i.e., psychologically irreducible) categories, and instead suggesting four.

  18. EMD-Based Symbolic Dynamic Analysis for the Recognition of Human and Nonhuman Pyroelectric Infrared Signals

    PubMed Central

    Zhao, Jiaduo; Gong, Weiguo; Tang, Yuzhen; Li, Weihong

    2016-01-01

    In this paper, we propose an effective human and nonhuman pyroelectric infrared (PIR) signal recognition method to reduce PIR detector false alarms. First, using the mathematical model of the PIR detector, we analyze the physical characteristics of the human and nonhuman PIR signals; second, based on the analysis results, we propose an empirical mode decomposition (EMD)-based symbolic dynamic analysis method for the recognition of human and nonhuman PIR signals. In the proposed method, first, we extract the detailed features of a PIR signal into five symbol sequences using an EMD-based symbolization method, then, we generate five feature descriptors for each PIR signal through constructing five probabilistic finite state automata with the symbol sequences. Finally, we use a weighted voting classification strategy to classify the PIR signals with their feature descriptors. Comparative experiments show that the proposed method can effectively classify the human and nonhuman PIR signals and reduce PIR detector’s false alarms. PMID:26805837

  19. Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression.

    PubMed

    Shen, Shensi; Rodrigo, Guillermo; Prakash, Satya; Majer, Eszter; Landrain, Thomas E; Kirov, Boris; Daròs, José-Antonio; Jaramillo, Alfonso

    2015-05-26

    Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves the de novo design of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA-RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits.

  20. Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression

    PubMed Central

    Shen, Shensi; Rodrigo, Guillermo; Prakash, Satya; Majer, Eszter; Landrain, Thomas E.; Kirov, Boris; Daròs, José-Antonio; Jaramillo, Alfonso

    2015-01-01

    Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves the de novo design of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA–RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits. PMID:25916845

  1. EMD-Based Symbolic Dynamic Analysis for the Recognition of Human and Nonhuman Pyroelectric Infrared Signals.

    PubMed

    Zhao, Jiaduo; Gong, Weiguo; Tang, Yuzhen; Li, Weihong

    2016-01-20

    In this paper, we propose an effective human and nonhuman pyroelectric infrared (PIR) signal recognition method to reduce PIR detector false alarms. First, using the mathematical model of the PIR detector, we analyze the physical characteristics of the human and nonhuman PIR signals; second, based on the analysis results, we propose an empirical mode decomposition (EMD)-based symbolic dynamic analysis method for the recognition of human and nonhuman PIR signals. In the proposed method, first, we extract the detailed features of a PIR signal into five symbol sequences using an EMD-based symbolization method, then, we generate five feature descriptors for each PIR signal through constructing five probabilistic finite state automata with the symbol sequences. Finally, we use a weighted voting classification strategy to classify the PIR signals with their feature descriptors. Comparative experiments show that the proposed method can effectively classify the human and nonhuman PIR signals and reduce PIR detector's false alarms.

  2. Requirements for implementation of Kuessner and Wagner indicial lift growth functions into the FLEXSTAB computer program system for use in dynamic loads analyses

    NASA Technical Reports Server (NTRS)

    Miller, R. D.; Rogers, J. T.

    1975-01-01

    General requirements for dynamic loads analyses are described. The indicial lift growth function unsteady subsonic aerodynamic representation is reviewed, and the FLEXSTAB CPS is evaluated with respect to these general requirements. The effects of residual flexibility techniques on dynamic loads analyses are also evaluated using a simple dynamic model.

  3. Analysis of Dynamic Stall Through Chirp Signal Pitch Excursions

    NASA Astrophysics Data System (ADS)

    Heintz, Kyle; Coleman, Dustin; Wicks, Michael; Corke, Thomas; Thomas, Flint

    2013-11-01

    An augmentation of the typical pitching airfoil experiment has been performed where the pitching frequency and amplitude are dynamically varied in a short-time event to produce a ``chirp'' trajectory, α (t) =α0 +α1 (t) sin (tω (t)) . The frequency evolution followed a Schroeder-phase relation, ω (t) =ωmin + K (ωmax -ωmin) . The frequencies ranged from 0.5 Hz to 30 Hz, resulting in reduced frequencies from 0.02 to 0.1. The free-stream Mach number ranged from Mach 0.4 to 0.6, giving chord Reynolds numbers from 5 ×105 to 3 ×106 . The airfoil was a NACA 23012 section shape that was fully instrumented with 31 flush-mounted high-bandwidth pressure transducers. The pressure transducer outputs were simultaneously sampled with the instantaneous angle of attack, α (t) . The motivation for this study was to compare dynamic stall under non-equilibrium conditions. A particular interest is on the flow features that occur when dynamically passing between light and deep stall regimes. The results include phase analysis of aerodynamic loads, wavelet-based spectral analysis, and the determination of the intra-cycle aerodynamic damping factors.

  4. Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module.

    PubMed

    Toettcher, Jared E; Weiner, Orion D; Lim, Wendell A

    2013-12-05

    The complex, interconnected architecture of cell-signaling networks makes it challenging to disentangle how cells process extracellular information to make decisions. We have developed an optogenetic approach to selectively activate isolated intracellular signaling nodes with light and use this method to follow the flow of information from the signaling protein Ras. By measuring dose and frequency responses in single cells, we characterize the precision, timing, and efficiency with which signals are transmitted from Ras to Erk. Moreover, we elucidate how a single pathway can specify distinct physiological outcomes: by combining distinct temporal patterns of stimulation with proteomic profiling, we identify signaling programs that differentially respond to Ras dynamics, including a paracrine circuit that activates STAT3 only after persistent (>1 hr) Ras activation. Optogenetic stimulation provides a powerful tool for analyzing the intrinsic transmission properties of pathway modules and identifying how they dynamically encode distinct outcomes.

  5. Calculation of intravascular signal in dynamic contrast enhanced-MRI using adaptive complex independent component analysis.

    PubMed

    Mehrabian, Hatef; Chopra, Rajiv; Martel, Anne L

    2013-04-01

    Assessing tumor response to therapy is a crucial step in personalized treatments. Pharmacokinetic (PK) modeling provides quantitative information about tumor perfusion and vascular permeability that are associated with prognostic factors. A fundamental step in most PK analyses is calculating the signal that is generated in the tumor vasculature. This signal is usually inseparable from the extravascular extracellular signal. It was shown previously using in vivo and phantom experiments that independent component analysis (ICA) is capable of calculating the intravascular time-intensity curve in dynamic contrast enhanced (DCE)-MRI. A novel adaptive complex independent component analysis (AC-ICA) technique is developed in this study to calculate the intravascular time-intensity curve and separate this signal from the DCE-MR images of tumors. The use of the complex-valued DCE-MRI images rather than the commonly used magnitude images satisfied the fundamental assumption of ICA, i.e., linear mixing of the sources. Using an adaptive cost function in ICA through estimating the probability distribution of the tumor vasculature at each iteration resulted in a more robust and accurate separation algorithm. The AC-ICA algorithm provided a better estimate for the intravascular time-intensity curve than the previous ICA-based method. A simulation study was also developed in this study to realistically simulate DCE-MRI data of a leaky tissue mimicking phantom. The passage of the MR contrast agent through the leaky phantom was modeled with finite element analysis using a diffusion model. Once the distribution of the contrast agent in the imaging field of view was calculated, DCE-MRI data was generated by solving the Bloch equation for each voxel at each time point. The intravascular time-intensity curve calculation results were compared to the previously proposed ICA-based intravascular time-intensity curve calculation method that applied ICA to the magnitude of the DCE-MRI data

  6. Dynamical system modeling via signal reduction and neural network simulation

    SciTech Connect

    Paez, T.L.; Hunter, N.F.

    1997-11-01

    Many dynamical systems tested in the field and the laboratory display significant nonlinear behavior. Accurate characterization of such systems requires modeling in a nonlinear framework. One construct forming a basis for nonlinear modeling is that of the artificial neural network (ANN). However, when system behavior is complex, the amount of data required to perform training can become unreasonable. The authors reduce the complexity of information present in system response measurements using decomposition via canonical variate analysis. They describe a method for decomposing system responses, then modeling the components with ANNs. A numerical example is presented, along with conclusions and recommendations.

  7. Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome

    PubMed Central

    Oliveira, Ana Paula; Dimopoulos, Sotiris; Busetto, Alberto Giovanni; Christen, Stefan; Dechant, Reinhard; Falter, Laura; Haghir Chehreghani, Morteza; Jozefczuk, Szymon; Ludwig, Christina; Rudroff, Florian; Schulz, Juliane Caroline; González, Asier; Soulard, Alexandre; Stracka, Daniele; Aebersold, Ruedi; Buhmann, Joachim M; Hall, Michael N; Peter, Matthias; Sauer, Uwe; Stelling, Jörg

    2015-01-01

    Cells react to nutritional cues in changing environments via the integrated action of signaling, transcriptional, and metabolic networks. Mechanistic insight into signaling processes is often complicated because ubiquitous feedback loops obscure causal relationships. Consequently, the endogenous inputs of many nutrient signaling pathways remain unknown. Recent advances for system-wide experimental data generation have facilitated the quantification of signaling systems, but the integration of multi-level dynamic data remains challenging. Here, we co-designed dynamic experiments and a probabilistic, model-based method to infer causal relationships between metabolism, signaling, and gene regulation. We analyzed the dynamic regulation of nitrogen metabolism by the target of rapamycin complex 1 (TORC1) pathway in budding yeast. Dynamic transcriptomic, proteomic, and metabolomic measurements along shifts in nitrogen quality yielded a consistent dataset that demonstrated extensive re-wiring of cellular networks during adaptation. Our inference method identified putative downstream targets of TORC1 and putative metabolic inputs of TORC1, including the hypothesized glutamine signal. The work provides a basis for further mechanistic studies of nitrogen metabolism and a general computational framework to study cellular processes. PMID:25888284

  8. Nonlinear dynamics approach to speech detection in noisy signals

    NASA Astrophysics Data System (ADS)

    Bronakowski, Lukasz J.

    2009-06-01

    The presented paper describes a novel approach to detection of speech corrupted by noise. The proposed procedure is based on fractal dimension, which is being evaluated directly from speech signal samples using two different methods: box-counting and the approach proposed by Katz. The recordings, taken from TIMIT database, were corrupted by five different types of noise (white, pink, hf-channel, babble and factory) with four noise amplitudes (5,10,15,20 dB). The resulting noisy speech was the subject of the analysis. The Otsu's method was used to determine a threshold value for differentiating between noise-only and noisy-speech segments. It has been shown that fractal dimension-based approach provides good basis for detecting speech under a presence of noise.

  9. MANIFOLD LEARNING FOR ANALYSIS OF LOW-ORDER NONLINEAR DYNAMICS IN HIGH-DIMENSIONAL ELECTROCARDIOGRAPHIC SIGNALS.

    PubMed

    Erem, B; Stovicek, P; Brooks, D H

    2012-07-12

    The dynamical structure of electrical recordings from the heart or torso surface is a valuable source of information about cardiac physiological behavior. In this paper, we use an existing data-driven technique for manifold identification to reveal electrophysiologically significant changes in the underlying dynamical structure of these signals. Our results suggest that this analysis tool characterizes and differentiates important parameters of cardiac bioelectric activity through their dynamic behavior, suggesting the potential to serve as an effective dynamic constraint in the context of inverse solutions.

  10. Characterizing the Response of Commercial and Industrial Facilities to Dynamic Pricing Signals from the Utility

    SciTech Connect

    Mathieu, Johanna L.; Gadgil, Ashok J.; Callaway, Duncan S.; Price, Phillip N.; Kiliccote, Sila

    2010-07-01

    We describe a method to generate statistical models of electricity demand from Commercial and Industrial (C&I) facilities including their response to dynamic pricing signals. Models are built with historical electricity demand data. A facility model is the sum of a baseline demand model and a residual demand model; the latter quantifies deviations from the baseline model due to dynamic pricing signals from the utility. Three regression-based baseline computation methods were developed and analyzed. All methods performed similarly. To understand the diversity of facility responses to dynamic pricing signals, we have characterized the response of 44 C&I facilities participating in a Demand Response (DR) program using dynamic pricing in California (Pacific Gas and Electric's Critical Peak Pricing Program). In most cases, facilities shed load during DR events but there is significant heterogeneity in facility responses. Modeling facility response to dynamic price signals is beneficial to the Independent System Operator for scheduling supply to meet demand, to the utility for improving dynamic pricing programs, and to the customer for minimizing energy costs.

  11. Spatio-temporal dynamics of a cell signal pathway with negative feedbacks: the MAPK/ERK pathway.

    PubMed

    Maya-Bernal, José Luis; Ramírez-Santiago, Guillermo

    2016-03-01

    We studied the spatio-temporal dynamics of a cell signal cascade with negative feedback that quantitatively emulates the regulative process that occurs in the Mitogen Activated Protein Kinase/Extracellular Regulated Kinase (MAPK/ERK) pathway. The model consists of a set of six coupled reaction-diffusion equations that describes the dynamics of the six-module pathway. In the basic module the active form of the protein transmits the signal to the next pathway’s module. As suggested by experiments, the model considers that the fifth module's kinase down-regulates the first and third modules. The feedback parameter is defined as, μ(r)( j)= k(kin)5/k(kin)(j), (j = 1, 3). We analysed the pathway's dynamics for μ(r)( j) = 0.10, 1.0, and 10 in the kinetic regimes: i) saturation of both kinases and phosphatases, ii) saturation of the phosphatases and iii) saturation of the kinases. For a regulated pathway the Total Activated Protein Profiles (TAPPs) as a function of time develop a maximum during the transient stage in the three kinetic regimes. These maxima become higher and their positions shift to longer times downstream. This scenario also applies to the TAPP's regulatory kinase that sums up its inhibitory action to that of the phosphatases leading to a maximum. Nevertheless, when μ(r)(j)= 1.0 , the TAPPs develop two maxima, with the second maximum being almost imperceptible. These results are in qualitative agreement with experimental data obtained from NIH 3T3 mouse fibroblasts. In addition, analyses of the stationary states as a function of position indicate that in the kinetic regime i) which is of physiological interest, signal transduction occurs with a relatively large propagation length for the three values of the regulative parameter. However, for μ(r)(j)= 0.10 , the sixth module concentration profile is transmitted with approximately 45% of its full value. The results obtained for μ(r)(j) = 10 , indicate that the first five concentration profiles are

  12. A divergent canonical WNT-signaling pathway regulates microtubule dynamics

    PubMed Central

    Ciani, Lorenza; Krylova, Olga; Smalley, Matthew J.; Dale, Trevor C.; Salinas, Patricia C.

    2004-01-01

    Dishevelled (DVL) is associated with axonal microtubules and regulates microtubule stability through the inhibition of the serine/threonine kinase, glycogen synthase kinase 3β (GSK-3β). In the canonical WNT pathway, the negative regulator Axin forms a complex with β-catenin and GSK-3β, resulting in β-catenin degradation. Inhibition of GSK-3β by DVL increases β-catenin stability and TCF transcriptional activation. Here, we show that Axin associates with microtubules and unexpectedly stabilizes microtubules through DVL. In turn, DVL stabilizes microtubules by inhibiting GSK-3β through a transcription- and β-catenin–independent pathway. More importantly, axonal microtubules are stabilized after DVL localizes to axons. Increased microtubule stability is correlated with a decrease in GSK-3β–mediated phosphorylation of MAP-1B. We propose a model in which Axin, through DVL, stabilizes microtubules by inhibiting a pool of GSK-3β, resulting in local changes in the phosphorylation of cellular targets. Our data indicate a bifurcation in the so-called canonical WNT-signaling pathway to regulate microtubule stability. PMID:14734535

  13. Aeroelastic and dynamic finite element analyses of a bladder shrouded disk

    NASA Technical Reports Server (NTRS)

    Smith, G. C. C.; Elchuri, V.

    1980-01-01

    The delivery and demonstration of a computer program for the analysis of aeroelastic and dynamic properties is reported. Approaches to flutter and forced vibration of mistuned discs, and transient aerothermoelasticity are described.

  14. Performance Analysis of Control Signal Transmission Technique for Cognitive Radios in Dynamic Spectrum Access Networks

    NASA Astrophysics Data System (ADS)

    Sakata, Ren; Tomioka, Tazuko; Kobayashi, Takahiro

    When cognitive radio (CR) systems dynamically use the frequency band, a control signal is necessary to indicate which carrier frequencies are currently available in the network. In order to keep efficient spectrum utilization, this control signal also should be transmitted based on the channel conditions. If transmitters dynamically select carrier frequencies, receivers have to receive control signals without knowledge of their carrier frequencies. To enable such transmission and reception, this paper proposes a novel scheme called DCPT (Differential Code Parallel Transmission). With DCPT, receivers can receive low-rate information with no knowledge of the carrier frequencies. The transmitter transmits two signals whose carrier frequencies are spaced by a predefined value. The absolute values of the carrier frequencies can be varied. When the receiver acquires the DCPT signal, it multiplies the signal by a frequency-shifted version of the signal; this yields a DC component that represents the data signal which is then demodulated. The performance was evaluated by means of numerical analysis and computer simulation. We confirmed that DCPT operates successfully even under severe interference if its parameters are appropriately configured.

  15. Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling.

    PubMed

    Mattila, Pieta K; Batista, Facundo D; Treanor, Bebhinn

    2016-02-01

    Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival.

  16. Integrated Strategies to Gain a Systems-Level View of Dynamic Signaling Networks.

    PubMed

    Newman, Robert H; Zhang, Jin

    2017-01-01

    In order to survive and function properly in the face of an ever changing environment, cells must be able to sense changes in their surroundings and respond accordingly. Cells process information about their environment through complex signaling networks composed of many discrete signaling molecules. Individual pathways within these networks are often tightly integrated and highly dynamic, allowing cells to respond to a given stimulus (or, as is typically the case under physiological conditions, a combination of stimuli) in a specific and appropriate manner. However, due to the size and complexity of many cellular signaling networks, it is often difficult to predict how cellular signaling networks will respond under a particular set of conditions. Indeed, crosstalk between individual signaling pathways may lead to responses that are nonintuitive (or even counterintuitive) based on examination of the individual pathways in isolation. Therefore, to gain a more comprehensive view of cell signaling processes, it is important to understand how signaling networks behave at the systems level. This requires integrated strategies that combine quantitative experimental data with computational models. In this chapter, we first examine some of the progress that has recently been made toward understanding the systems-level regulation of cellular signaling networks, with a particular emphasis on phosphorylation-dependent signaling networks. We then discuss how genetically targetable fluorescent biosensors are being used together with computational models to gain unique insights into the spatiotemporal regulation of signaling networks within single, living cells.

  17. Dynamic Range Enhancement of High-Speed Electrical Signal Data via Non-Linear Compression

    NASA Technical Reports Server (NTRS)

    Laun, Matthew C. (Inventor)

    2016-01-01

    Systems and methods for high-speed compression of dynamic electrical signal waveforms to extend the measuring capabilities of conventional measuring devices such as oscilloscopes and high-speed data acquisition systems are discussed. Transfer function components and algorithmic transfer functions can be used to accurately measure signals that are within the frequency bandwidth but beyond the voltage range and voltage resolution capabilities of the measuring device.

  18. Dynamic modes of microwave signal autogeneration in a radio photonic ring generator

    NASA Astrophysics Data System (ADS)

    Kondrashov, A. V.; Ustinov, A. B.; Kalinikos, B. A.

    2017-02-01

    Dynamic modes of microwave signal autogeneration in a radio photonic generator have been investigated. The generator is a ring circuit with a low-pass filter and microwave amplifier in its microwave path. The optical path contains an optical fiber delay line. The generator demonstrates the periodical, chaotic, and noise dynamics. It has been shown that the correlation dimensionality of the random signal attractor in the chaotic generation mode saturates with increasing phase space dimensionality. Saturation is not observed in the noise-generation mode.

  19. A dynamic scanning method based on signal-statistics for scanning electron microscopy.

    PubMed

    Timischl, F

    2014-01-01

    A novel dynamic scanning method for noise reduction in scanning electron microscopy and related applications is presented. The scanning method dynamically adjusts the scanning speed of the electron beam depending on the statistical behavior of the detector signal and gives SEM images with uniform and predefined standard deviation, independent of the signal value itself. In the case of partially saturated images, the proposed method decreases image acquisition time without sacrificing image quality. The effectiveness of the proposed method is shown and compared to the conventional scanning method and median filtering using numerical simulations.

  20. Extracting protein dynamics information from overlapped NMR signals using relaxation dispersion difference NMR spectroscopy.

    PubMed

    Konuma, Tsuyoshi; Harada, Erisa; Sugase, Kenji

    2015-12-01

    Protein dynamics plays important roles in many biological events, such as ligand binding and enzyme reactions. NMR is mostly used for investigating such protein dynamics in a site-specific manner. Recently, NMR has been actively applied to large proteins and intrinsically disordered proteins, which are attractive research targets. However, signal overlap, which is often observed for such proteins, hampers accurate analysis of NMR data. In this study, we have developed a new methodology called relaxation dispersion difference that can extract conformational exchange parameters from overlapped NMR signals measured using relaxation dispersion spectroscopy. In relaxation dispersion measurements, the signal intensities of fluctuating residues vary according to the Carr-Purcell-Meiboon-Gill pulsing interval, whereas those of non-fluctuating residues are constant. Therefore, subtraction of each relaxation dispersion spectrum from that with the highest signal intensities, measured at the shortest pulsing interval, leaves only the signals of the fluctuating residues. This is the principle of the relaxation dispersion difference method. This new method enabled us to extract exchange parameters from overlapped signals of heme oxygenase-1, which is a relatively large protein. The results indicate that the structural flexibility of a kink in the heme-binding site is important for efficient heme binding. Relaxation dispersion difference requires neither selectively labeled samples nor modification of pulse programs; thus it will have wide applications in protein dynamics analysis.

  1. Context-dependent dynamic UV signaling in female three spine sticklebacks

    PubMed Central

    Hiermes, Meike; Bakker, Theo C. M.; Mehlis, Marion; Rick, Ingolf P.

    2015-01-01

    Color signals, including ultraviolet (UV) signals, are widespread throughout the animal kingdom and color changes can be influenced by reproductive and motivational state. However, studies on dynamic changes of UV signals are scarce. Three spine sticklebacks (Gasterosteus aculeatus) that show intraspecific UV communication were used to study dynamic UV signaling in females. Reflectance measurements were taken from the distended abdomen, which serves as signal of female fecundity and readiness to spawn for courting males, and the melanized dorsal region. Scans were taken during egg maturation as well as before and after stimulation with a male to investigate context-dependent color changes. We used a physiological model of vision to determine how females might be perceived by conspecifics and quantified chromatic contrasts among both body regions and between body regions and the background for all stages. Females showed a significant increase in abdominal UV intensity during egg maturation and in response to a courting male. Measures of chromatic contrast among body regions (abdomen vs. dorsal region) and against the background (abdomen vs. background) were also increased during egg maturation and in response to the male stimulus (abdomen vs. background). Our results provide evidence for dynamic UV signaling in females in a reproductive context. PMID:26658986

  2. Context-dependent dynamic UV signaling in female three spine sticklebacks.

    PubMed

    Hiermes, Meike; Bakker, Theo C M; Mehlis, Marion; Rick, Ingolf P

    2015-12-10

    Color signals, including ultraviolet (UV) signals, are widespread throughout the animal kingdom and color changes can be influenced by reproductive and motivational state. However, studies on dynamic changes of UV signals are scarce. Three spine sticklebacks (Gasterosteus aculeatus) that show intraspecific UV communication were used to study dynamic UV signaling in females. Reflectance measurements were taken from the distended abdomen, which serves as signal of female fecundity and readiness to spawn for courting males, and the melanized dorsal region. Scans were taken during egg maturation as well as before and after stimulation with a male to investigate context-dependent color changes. We used a physiological model of vision to determine how females might be perceived by conspecifics and quantified chromatic contrasts among both body regions and between body regions and the background for all stages. Females showed a significant increase in abdominal UV intensity during egg maturation and in response to a courting male. Measures of chromatic contrast among body regions (abdomen vs. dorsal region) and against the background (abdomen vs. background) were also increased during egg maturation and in response to the male stimulus (abdomen vs. background). Our results provide evidence for dynamic UV signaling in females in a reproductive context.

  3. Nonlinear dynamic behavior of the human knee joint--Part I: Postmortem frequency domain analyses.

    PubMed

    Dortmans, L; Jans, H; Sauren, A; Huson, A

    1991-11-01

    Characteristics results of postmortem experiments on five knee-joint specimens are reported. The experiments were performed to investigate the applicability of a local linearization technique that would make it possible to describe the dynamic behavior of the joint in terms of transfer functions. The results indicate that the stiffness of the bracing wires, attached to muscle tendons to create a static equilibrium position, can be accounted for when determining the stiffness of the joint. Besides the static equilibrium configuration, the magnitude of the dynamic load and the type of dynamic load applied to the joint can be shown to have their influence. As the influence of the dynamic load is significant, it has to be concluded that in essence the knee joint has to be regarded as a nonlinear system, making application of a Local Linearization Technique questionable. However, when the magnitude of the dynamic load is included as an additional measurement parameter, an indication can be obtained about the behavior of the joint and the degree of nonlinearity.

  4. Correlation of ground tests and analyses of a dynamically scaled Space Station model configuration

    NASA Technical Reports Server (NTRS)

    Javeed, Mehzad; Edighoffer, Harold H.; Mcgowan, Paul E.

    1993-01-01

    Verification of analytical models through correlation with ground test results of a complex space truss structure is demonstrated. A multi-component, dynamically scaled space station model configuration is the focus structure for this work. Previously established test/analysis correlation procedures are used to develop improved component analytical models. Integrated system analytical models, consisting of updated component analytical models, are compared with modal test results to establish the accuracy of system-level dynamic predictions. Design sensitivity model updating methods are shown to be effective for providing improved component analytical models. Also, the effects of component model accuracy and interface modeling fidelity on the accuracy of integrated model predictions is examined.

  5. Correlation of ground tests and analyses of a dynamically scaled space station model configuration

    NASA Technical Reports Server (NTRS)

    Javeed, Mehzad; Edighoffer, Harold H.; Mcgowan, Paul E.

    1993-01-01

    Verification of analytical models through correlation with ground test results of a complex space truss structure is demonstrated. A multi-component, dynamically scaled space station model configuration is the focus structure for this work. Previously established test/analysis correlation procedures are used to develop improved component analytical models. Integrated system analytical models, consisting of updated component analytical models, are compared with modal test results to establish the accuracy of system-level dynamic predictions. Design sensitivity model updating methods are shown to be effective for providing improved component analytical models. Also, the effects of component model accuracy and interface modeling fidelity on the accuracy of integrated model predictions is examined.

  6. European Space Agency's launcher multibody dynamics simulator used for system and subsystem level analyses

    NASA Astrophysics Data System (ADS)

    Baldesi, Gianluigi; Toso, Mario

    2012-06-01

    Virtual simulation is currently a key activity in the specification, design, verification and operations of space systems. System modelling and simulation support in fact a number of use cases across the spacecraft development life cycle, including activities such as system design validation, software verification and validation, spacecraft unit and sub-system test activities, etc. As the reliance on virtual modelling, simulation and justification has substantially grown in recent years, a more coordinated and consistent approach to the development of such simulation tools across project phases can bring substantial benefit in reducing the overall space programme schedule, risk and cost. By capitalizing on the ESA (European Space Agency) Structures and Mechanisms division's strong expertise in dynamics (multibody software), a generic multibody flight simulator was created to simulate a wide variety of launch vehicle dynamics and control problems at system level since 2001. The backbone of the multibody dynamics simulator is DCAP (Dynamic and Control Analysis Package), a multibody software, developed by ESA together with industry, with more than 30 years heritage in space applications. This software is a suite of fast, effective computer programs that provides the user with capabilities to model, simulate and analyze the dynamics and control performances of coupled rigid and flexible structural systems subjected to possibly time-varying structural characteristics and space environmental loads. The simulator uses the formulation for the dynamics of multi-rigid/flexible-body systems based on Order( n) algorithm. This avoids the explicit computation of a global mass matrix and its inversion, and the computational burden in these schemes increases only linearly with the number n of the system's degrees of freedom. A dedicated symbolic manipulation pre-processor is then used in the coding optimization. With the implementation of dedicated interfaces to other specialised

  7. Ongoing Analyses of Rocket Based Combined Cycle Engines by the Applied Fluid Dynamics Analysis Group at Marshall Space Flight Center

    NASA Technical Reports Server (NTRS)

    Ruf, Joseph H.; Holt, James B.; Canabal, Francisco

    2001-01-01

    This paper presents the status of analyses on three Rocket Based Combined Cycle (RBCC) configurations underway in the Applied Fluid Dynamics Analysis Group (TD64). TD64 is performing computational fluid dynamics (CFD) analysis on a Penn State RBCC test rig, the proposed Draco axisymmetric RBCC engine and the Trailblazer engine. The intent of the analysis on the Penn State test rig is to benchmark the Finite Difference Navier Stokes (FDNS) code for ejector mode fluid dynamics. The Draco analysis was a trade study to determine the ejector mode performance as a function of three engine design variables. The Trailblazer analysis is to evaluate the nozzle performance in scramjet mode. Results to date of each analysis are presented.

  8. Dynamic interactions mediated by nonredundant signaling mechanisms couple circadian clock neurons.

    PubMed

    Evans, Jennifer A; Leise, Tanya L; Castanon-Cervantes, Oscar; Davidson, Alec J

    2013-11-20

    Interactions among suprachiasmatic nucleus (SCN) neurons are required for robust circadian rhythms entrained to local time. To investigate these signaling mechanisms, we developed a functional coupling assay that uniquely captures the dynamic process by which SCN neurons interact. As a population, SCN neurons typically display synchronized rhythms with similar peak times, but will peak 6-12 hr apart after in vivo exposure to long days. Once they are removed from these conditions, SCN neurons resynchronize through a phase-dependent coupling process mediated by both vasoactive intestinal polypeptide (VIP) and GABAA signaling. Notably, GABAA signaling contributes to coupling when the SCN network is in an antiphase configuration, but opposes synchrony under steady-state conditions. Further, VIP acts together with GABAA signaling to couple the network in an antiphase configuration, but promotes synchrony under steady-state conditions by counteracting the actions of GABAA signaling. Thus, SCN neurons interact through nonredundant coupling mechanisms influenced by the state of the network.

  9. Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis.

    PubMed

    Fu, Jiang; Hsu, Wei

    2013-04-01

    A signal first arising in the dermis to initiate the development of hair follicles has been described for many decades. Wnt is the earliest signal known to be intimately involved in hair follicle induction. However, it is not clear whether the inductive signal of Wnt arises intradermally or intraepidermally. Whether Wnt acts as the first dermal signal to initiate hair follicle development also remains unclear. Here we report that Wnt production mediated by Gpr177, the mouse Wls ortholog, is essential for hair follicle induction. Gpr177, encoding a multipass transmembrane protein, regulates Wnt sorting and secretion. Cell type-specific abrogation of the signal reveals that only epidermal, but not dermal, production of Wnt is required. An intraepidermal Wnt signal is necessary and sufficient for hair follicle initiation. However, the subsequent development depends on reciprocal signaling crosstalk of epidermal and dermal cells. Wnt signals within the epidermis and dermis and crossing between the epidermis and dermis have distinct roles and specific functions in skin development. This study not only defines the cell type responsible for Wnt production, but also reveals a highly dynamic regulation of Wnt signaling at different steps of hair follicle morphogenesis. Our findings uncover a mechanism underlying hair follicle development orchestrated by the Wnt pathway.

  10. Global and local properties used as analyses tools for molecular-dynamics simulations

    NASA Astrophysics Data System (ADS)

    Bachlechner, Martina E.; Anderson, Jonas T.; Cao, Deng; Leonard, Robert H.; Owens, Eli T.; Schiffbauer, Jarrod E.; Burky, Melissa R.; Ducatman, Samuel C.; Guffey, Eric J.; Serrano Ramos2, Fernando

    2006-03-01

    Molecular dynamics simulations have been used to study mechanical failure in realistic interface materials. Averaging over the individual atoms' contributions yields local and global information including displacements, bond angles, strains, stress tensor components, and pair distribution functions. A combined analysis of global and local properties facilitates detailed insight in the mechanisms of failure, which will eventually guide on how to prevent failure of interfaces.

  11. Three-dimensional imaging system for analyses of dynamic droplet impaction and deposition formation on leaves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A system was developed to assess the dynamic processes of droplet impact, rebound and retention on leaf surfaces with three-dimensional (3-D) images. The system components consisted of a uniform-size droplet generator, two high speed digital video cameras, a constant speed track, a leaf holder, and ...

  12. Stat5 signaling specifies basal versus stress erythropoietic responses through distinct binary and graded dynamic modalities.

    PubMed

    Porpiglia, Ermelinda; Hidalgo, Daniel; Koulnis, Miroslav; Tzafriri, Abraham R; Socolovsky, Merav

    2012-08-01

    Erythropoietin (Epo)-induced Stat5 phosphorylation (p-Stat5) is essential for both basal erythropoiesis and for its acceleration during hypoxic stress. A key challenge lies in understanding how Stat5 signaling elicits distinct functions during basal and stress erythropoiesis. Here we asked whether these distinct functions might be specified by the dynamic behavior of the Stat5 signal. We used flow cytometry to analyze Stat5 phosphorylation dynamics in primary erythropoietic tissue in vivo and in vitro, identifying two signaling modalities. In later (basophilic) erythroblasts, Epo stimulation triggers a low intensity but decisive, binary (digital) p-Stat5 signal. In early erythroblasts the binary signal is superseded by a high-intensity graded (analog) p-Stat5 response. We elucidated the biological functions of binary and graded Stat5 signaling using the EpoR-HM mice, which express a "knocked-in" EpoR mutant lacking cytoplasmic phosphotyrosines. Strikingly, EpoR-HM mice are restricted to the binary signaling mode, which rescues these mice from fatal perinatal anemia by promoting binary survival decisions in erythroblasts. However, the absence of the graded p-Stat5 response in the EpoR-HM mice prevents them from accelerating red cell production in response to stress, including a failure to upregulate the transferrin receptor, which we show is a novel stress target. We found that Stat5 protein levels decline with erythroblast differentiation, governing the transition from high-intensity graded signaling in early erythroblasts to low-intensity binary signaling in later erythroblasts. Thus, using exogenous Stat5, we converted later erythroblasts into high-intensity graded signal transducers capable of eliciting a downstream stress response. Unlike the Stat5 protein, EpoR expression in erythroblasts does not limit the Stat5 signaling response, a non-Michaelian paradigm with therapeutic implications in myeloproliferative disease. Our findings show how the binary and

  13. Novel Method for Processing the Dynamic Calibration Signal of Pressure Sensor

    PubMed Central

    Wang, Zhongyu; Li, Qiang; Wang, Zhuoran; Yan, Hu

    2015-01-01

    Dynamic calibration is one of the important ways to acquire the dynamic performance parameters of a pressure sensor. This research focuses on the processing method for the output of calibrated pressure sensor, and mainly attempts to solve the problem of extracting the true information of step response under strong interference noise. A dynamic calibration system based on a shock tube is established to excite the time-domain response signal of a calibrated pressure sensor. A key processing on difference modeling is applied for the obtained signal, and several generating sequences are established. A fusion process for the generating sequences is then undertaken, and the true information of the step response of the calibrated pressure sensor can be obtained. Finally, by implementing the common QR decomposition method to deal with the true information, a dynamic model characterizing the dynamic performance of the calibrated pressure sensor is established. A typical pressure sensor was used to perform calibration tests and a frequency-domain experiment for the sensor was also conducted. Results show that the proposed method could effectively filter strong interference noise in the output of the sensor and the corresponding dynamic model could effectively characterize the dynamic performance of the pressure sensor. PMID:26197324

  14. Novel Method for Processing the Dynamic Calibration Signal of Pressure Sensor.

    PubMed

    Wang, Zhongyu; Li, Qiang; Wang, Zhuoran; Yan, Hu

    2015-07-21

    Dynamic calibration is one of the important ways to acquire the dynamic performance parameters of a pressure sensor. This research focuses on the processing method for the output of calibrated pressure sensor, and mainly attempts to solve the problem of extracting the true information of step response under strong interference noise. A dynamic calibration system based on a shock tube is established to excite the time-domain response signal of a calibrated pressure sensor. A key processing on difference modeling is applied for the obtained signal, and several generating sequences are established. A fusion process for the generating sequences is then undertaken, and the true information of the step response of the calibrated pressure sensor can be obtained. Finally, by implementing the common QR decomposition method to deal with the true information, a dynamic model characterizing the dynamic performance of the calibrated pressure sensor is established. A typical pressure sensor was used to perform calibration tests and a frequency-domain experiment for the sensor was also conducted. Results show that the proposed method could effectively filter strong interference noise in the output of the sensor and the corresponding dynamic model could effectively characterize the dynamic performance of the pressure sensor.

  15. Network dynamics for optimal compressive-sensing input-signal recovery.

    PubMed

    Barranca, Victor J; Kovačič, Gregor; Zhou, Douglas; Cai, David

    2014-10-01

    By using compressive sensing (CS) theory, a broad class of static signals can be reconstructed through a sequence of very few measurements in the framework of a linear system. For networks with nonlinear and time-evolving dynamics, is it similarly possible to recover an unknown input signal from only a small number of network output measurements? We address this question for pulse-coupled networks and investigate the network dynamics necessary for successful input signal recovery. Determining the specific network characteristics that correspond to a minimal input reconstruction error, we are able to achieve high-quality signal reconstructions with few measurements of network output. Using various measures to characterize dynamical properties of network output, we determine that networks with highly variable and aperiodic output can successfully encode network input information with high fidelity and achieve the most accurate CS input reconstructions. For time-varying inputs, we also find that high-quality reconstructions are achievable by measuring network output over a relatively short time window. Even when network inputs change with time, the same optimal choice of network characteristics and corresponding dynamics apply as in the case of static inputs.

  16. Network dynamics for optimal compressive-sensing input-signal recovery

    NASA Astrophysics Data System (ADS)

    Barranca, Victor J.; Kovačič, Gregor; Zhou, Douglas; Cai, David

    2014-10-01

    By using compressive sensing (CS) theory, a broad class of static signals can be reconstructed through a sequence of very few measurements in the framework of a linear system. For networks with nonlinear and time-evolving dynamics, is it similarly possible to recover an unknown input signal from only a small number of network output measurements? We address this question for pulse-coupled networks and investigate the network dynamics necessary for successful input signal recovery. Determining the specific network characteristics that correspond to a minimal input reconstruction error, we are able to achieve high-quality signal reconstructions with few measurements of network output. Using various measures to characterize dynamical properties of network output, we determine that networks with highly variable and aperiodic output can successfully encode network input information with high fidelity and achieve the most accurate CS input reconstructions. For time-varying inputs, we also find that high-quality reconstructions are achievable by measuring network output over a relatively short time window. Even when network inputs change with time, the same optimal choice of network characteristics and corresponding dynamics apply as in the case of static inputs.

  17. Quantum dot SOA input power dynamic range improvement for differential-phase encoded signals.

    PubMed

    Vallaitis, T; Bonk, R; Guetlein, J; Hillerkuss, D; Li, J; Brenot, R; Lelarge, F; Duan, G H; Freude, W; Leuthold, J

    2010-03-15

    Experimentally we find a 10 dB input power dynamic range advantage for amplification of phase encoded signals with quantum dot SOA as compared to low-confinement bulk SOA. An analysis of amplitude and phase effects shows that this improvement can be attributed to the lower alpha-factor found in QD SOA.

  18. Dynamic changes in brewing yeast cells in culture revealed by statistical analyses of yeast morphological data.

    PubMed

    Ohnuki, Shinsuke; Enomoto, Kenichi; Yoshimoto, Hiroyuki; Ohya, Yoshikazu

    2014-03-01

    The vitality of brewing yeasts has been used to monitor their physiological state during fermentation. To investigate the fermentation process, we used the image processing software, CalMorph, which generates morphological data on yeast mother cells and bud shape, nuclear shape and location, and actin distribution. We found that 248 parameters changed significantly during fermentation. Successive use of principal component analysis (PCA) revealed several important features of yeast, providing insight into the dynamic changes in the yeast population. First, PCA indicated that much of the observed variability in the experiment was summarized in just two components: a change with a peak and a change over time. Second, PCA indicated the independent and important morphological features responsible for dynamic changes: budding ratio, nucleus position, neck position, and actin organization. Thus, the large amount of data provided by imaging analysis can be used to monitor the fermentation processes involved in beer and bioethanol production.

  19. Kinematic and dynamic analyses of the Stanford/JPL robot hand. [MACSYMA

    SciTech Connect

    Johnson, V.J.; Starr, G.P.

    1987-11-01

    This report develops the kinematic and dynamic equations for one finger of the three-fingered Stanford/JPL robot hand and documents the physical parameters needed to implement the equations. The equations can be used in control schemes for position and force control of the Stanford/JPL robot hand. The output file for the MACSYMA program is given. 4 refs., 6 figs., 1 tab.

  20. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure

    SciTech Connect

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-07

    Nuclear quantum effects play a dominant role in determining the phase diagram of H{sub 2}. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H{sub 2} under vapor pressure, demonstrating the difference from liquid and high-pressure solid H{sub 2}. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H{sub 2} molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H–H vibrational frequencies as well as H–H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H{sub 2} solid will be useful in monitoring thermodynamic states of condensed hydrogens.

  1. Toward global modelling approaches for dynamic analyses of rotating assemblies of turbomachines

    NASA Astrophysics Data System (ADS)

    Chatelet, Eric; D'Ambrosio, Flavio; Jacquet-Richardet, Georges

    2005-04-01

    It is now increasingly necessary to predict accurately, at the design stage and without excessive computer costs, the dynamic behavior of rotating parts of turbomachines, in order to be able to avoid resonant conditions at operating speeds. Classical approaches are based on different uncoupled models. For example, rotordynamics deals with the shaft behavior while bladed assemblies dynamics deals with wheels, and the possibility of interaction between those elements is generally not analyzed. In this study, the global non-rotating mode shapes of flexible bladed disc-shaft assemblies are used in a modal analysis method for calculating the dynamic characteristics (frequencies and mode shapes) of the corresponding rotating system. The non-rotating mode shapes are computed using a finite element cyclic symmetry approach. Rotational effects, such as centrifugal stiffening and gyroscopic effects, are accounted for. All the possible couplings between the flexible parts and every kind of deformations are allowed. The proposed model is applied to a thin-walled composite shaft and to a turbomolecular pump rotating assembly. The results obtained illustrate clearly some of the limitations of classical approaches.

  2. Accuracy in dynamic laser speckle: optimum size of speckles for temporal and frequency analyses

    NASA Astrophysics Data System (ADS)

    Braga, Roberto A.; González-Peña, Rolando J.

    2016-12-01

    The dynamic laser-speckle phenomenon has been used as a potential tool to monitor the activity of many biological and nonbiological samples; however, a key tailoring of the experimental configuration must be taken into account to avoid wrong measurements, since the general rules addressed to speckle as information cannot be directly adopted in dynamic laser-speckle monitoring. The speckle/pixel size ratio is provided by the f-number and by the magnification of the macro lens, and attention is mainly directed toward adjusting a speckle/pixel ratio higher than 1. However, a speckle/pixel ratio much higher than one does not mean an optimum adjustment. This work tested different apertures with fixed magnification yielding to monitor a drying paint process. The outcomes were evaluated in the time and frequency domains. The highest speckle/pixel size ratio was not the best to monitor the process using the dynamic laser speckle under frequency analysis. Tailoring of the devices must take into account the optimum speckle/pixel size ratio, which could vary depending on the application, and the known Nyquist theorem cannot be considered as a sufficient condition since the setup of the optical camera with its macro and iris must also be adjusted in accordance with the frequency response.

  3. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure.

    PubMed

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-07

    Nuclear quantum effects play a dominant role in determining the phase diagram of H2. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H2 under vapor pressure, demonstrating the difference from liquid and high-pressure solid H2. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H2 molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H-H vibrational frequencies as well as H-H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H2 solid will be useful in monitoring thermodynamic states of condensed hydrogens.

  4. Effective Boolean dynamics analysis to identify functionally important genes in large-scale signaling networks.

    PubMed

    Trinh, Hung-Cuong; Kwon, Yung-Keun

    2015-11-01

    Efficiently identifying functionally important genes in order to understand the minimal requirements of normal cellular development is challenging. To this end, a variety of structural measures have been proposed and their effectiveness has been investigated in recent literature; however, few studies have shown the effectiveness of dynamics-based measures. This led us to investigate a dynamic measure to identify functionally important genes, and the effectiveness of which was verified through application on two large-scale human signaling networks. We specifically consider Boolean sensitivity-based dynamics against an update-rule perturbation (BSU) as a dynamic measure. Through investigations on two large-scale human signaling networks, we found that genes with relatively high BSU values show slower evolutionary rate and higher proportions of essential genes and drug targets than other genes. Gene-ontology analysis showed clear differences between the former and latter groups of genes. Furthermore, we compare the identification accuracies of essential genes and drug targets via BSU and five well-known structural measures. Although BSU did not always show the best performance, it effectively identified the putative set of genes, which is significantly different from the results obtained via the structural measures. Most interestingly, BSU showed the highest synergy effect in identifying the functionally important genes in conjunction with other measures. Our results imply that Boolean-sensitive dynamics can be used as a measure to effectively identify functionally important genes in signaling networks.

  5. Single-Molecule Study of Protein-Protein Interaction Dynamics in a Cell Signaling System

    SciTech Connect

    Tan, Xin; Nalbant, Perihan; Toutchkine, Alexei; Hu, Dehong; Vorpagel, Erich R.; Hahn, Klaus M.; Lu, H PETER.

    2004-01-15

    We report a combined single-molecule fluorescence and molecular dynamics (MD) simulation study of protein-protein interactions in a GTP-binding intracellular signaling protein Cdc42 in complex with a downstream effector protein WASP. A 13- kDa WASP fragment which binds only the activated GTP-loaded Cdc42 was labeled with a novel solvatochromic dye and used to probe hydrophobic interactions significant to Cdc42/WASP recognition. Our single-molecule fluorescence measurements have shown conformational fluctuations of the protein complex and suggested multiple conformational states at a wide range of time scales might be involved in protein interaction dynamics. Single-molecule experiments have revealed the dynamic disorder or protein-protein interactions within the Cdc42/WASP complex, which may be important for regulating downstream signaling events.

  6. Single-Molecule Study of Protein-Protein Interaction Dynamics in a Cell Signaling System

    SciTech Connect

    Tan, Xin; Nalbant, Perihan; Toutchkine, Alexei; Hu, Dehong; Vorpagel, Erich R.; Hahn, Klaus M.; Lu, H. Peter

    2004-01-01

    We report a study on protein-protein noncovalent interactions in an intracellular signaling protein complex, using single-molecule spectroscopy and molecular dynamics (MD) simulations. A Wiskott-Aldrich Syndrome Protein (WASP) fragment that binds only the activated intracellular signaling protein Cdc42 was labeled with a novel solvatochromic dye and used to probe hydrophobic interactions significant to Cdc42/WASP recognition. The study shows static and dynamic inhomogeneous conformational fluctuations of the protein complex that involve bound and loosely bound states. A two-coupled, two-state Markovian kinetic model is proposed for the conformational dynamics. Finally, the MD simulations explore the origin of these conformational states and associated conformational fluctuations in this protein-protein interaction system.

  7. Discrete Dynamics Model for the Speract-Activated Ca2+ Signaling Network Relevant to Sperm Motility

    PubMed Central

    Espinal, Jesús; Aldana, Maximino; Guerrero, Adán; Wood, Christopher

    2011-01-01

    Understanding how spermatozoa approach the egg is a central biological issue. Recently a considerable amount of experimental evidence has accumulated on the relation between oscillations in intracellular calcium ion concentration ([Ca]) in the sea urchin sperm flagellum, triggered by peptides secreted from the egg, and sperm motility. Determination of the structure and dynamics of the signaling pathway leading to these oscillations is a fundamental problem. However, a biochemically based formulation for the comprehension of the molecular mechanisms operating in the axoneme as a response to external stimulus is still lacking. Based on experiments on the S. purpuratus sea urchin spermatozoa, we propose a signaling network model where nodes are discrete variables corresponding to the pathway elements and the signal transmission takes place at discrete time intervals according to logical rules. The validity of this model is corroborated by reproducing previous empirically determined signaling features. Prompted by the model predictions we performed experiments which identified novel characteristics of the signaling pathway. We uncovered the role of a high voltage-activated channel as a regulator of the delay in the onset of fluctuations after activation of the signaling cascade. This delay time has recently been shown to be an important regulatory factor for sea urchin sperm reorientation. Another finding is the participation of a voltage-dependent calcium-activated channel in the determination of the period of the fluctuations. Furthermore, by analyzing the spread of network perturbations we find that it operates in a dynamically critical regime. Our work demonstrates that a coarse-grained approach to the dynamics of the signaling pathway is capable of revealing regulatory sperm navigation elements and provides insight, in terms of criticality, on the concurrence of the high robustness and adaptability that the reproduction processes are predicted to have developed

  8. Dynamic analyses of a crack run-arrest experiment in a nonisothermal plate

    SciTech Connect

    Bass, B.R.; Pugh, C.E.; Stamm, H.K.

    1985-06-01

    In crack-arrest studies sponsored by the Heavy-Section Steel Technology (HSST) Program, a primary objective has been to produce fracture toughness data for reactor pressure vessel materials at temperatures approaching the Charpy upper-shelf regime. Wide-plate tests being conducted at the National Bureau of Standards for the HSST Program are providing an opportunity to obtain significant numbers of data points at affordable costs. In these tests, a single-edge crack in a wide-plate which is subjected to tensile loading initiates at low temperature and arrests in a region of increased fracture toughness. The gradient in toughness is achieved by applying a linear transverse temperature profile across the plate. The second test in this series for A 533 grade B class 1 steel involves crack initiation in cleavage followed by arrest at a temperature corresponding to Charpy upper-shelf behavior. The plate geometry, the material properties, and the instrumentation are discussed along with conditions and results for this test. Pretest static and elastodynamic analyses are described, and posttest analyses based on actual boundary conditions are shown to compare favorably with the observed run-arrest events.

  9. Membrane potential modulates plasma membrane phospholipid dynamics and K-Ras signaling

    PubMed Central

    Zhou, Yong; Wong, Ching-On; Cho, Kwang-jin; van der Hoeven, Dharini; Liang, Hong; Thakur, Dhananiay P.; Luo, Jialie; Babic, Milos; Zinsmaier, Konrad E.; Zhu, Michael X.; Hu, Hongzhen; Venkatachalam, Kartik; Hancock, John F.

    2015-01-01

    Plasma membrane depolarization can trigger cell proliferation, but how membrane potential influences mitogenic signaling is uncertain. Here, we show that plasma membrane depolarization induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K-Ras, which is targeted to the plasma membrane by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes in phosphatidylserine and K-Ras plasma membrane organization occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in vivo and robustly amplify K-Ras–dependent mitogen-activated protein kinase (MAPK) signaling. Conversely, plasma membrane repolarization disrupts K-Ras nanoclustering and inhibits MAPK signaling. By responding to voltage-induced changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up the plasma membrane as a biological field-effect transistor, allowing membrane potential to control the gain in mitogenic signaling circuits. PMID:26293964

  10. Dynamic characterization of a lightweight, highly maneuverable spacecraft using modal and finite element analyses

    SciTech Connect

    Manning, P.A.; Burdick, R.B.; Woehrle, T.G.

    1992-11-01

    The Lawrence Livermore National Laboratory is engaged in a technology development project which includes designing a lightweight, autonomous, highly maneuverable space vehicle, commonly referred to as a probe. The current probe design includes a guidance and control system that requires complete information on the dynamic response of the probe during operation. A finite element model of the probe was constructed to provide analytical information on the dynamic response to specific operational inputs. In order to verify the assumptions made in the model, a mass mock-up of the probe was constructed at LLNL and an experimental modal survey was performed to determine the frequencies, damping values and deflection shapes for each natural mode of the mock-up. The experimental modal parameters were compared with the parameters obtained through modal analysis of the finite element model to provide a measure of the correlation between the model and the actual structure. This report describes the experimental modal testing and analysis of the mass mock-up and compares the experimental results with the finite element results.

  11. The role of ecological dynamics in analysing performance in team sports.

    PubMed

    Vilar, Luís; Araújo, Duarte; Davids, Keith; Button, Chris

    2012-01-01

    Performance analysis is a subdiscipline of sports sciences and one-approach, notational analysis, has been used to objectively audit and describe behaviours of performers during different subphases of play, providing additional information for practitioners to improve future sports performance. Recent criticisms of these methods have suggested the need for a sound theoretical rationale to explain performance behaviours, not just describe them. The aim of this article was to show how ecological dynamics provides a valid theoretical explanation of performance in team sports by explaining the formation of successful and unsuccessful patterns of play, based on symmetry-breaking processes emerging from functional interactions between players and the performance environment. We offer the view that ecological dynamics is an upgrade to more operational methods of performance analysis that merely document statistics of competitive performance. In support of our arguments, we refer to exemplar data on competitive performance in team sports that have revealed functional interpersonal interactions between attackers and defenders, based on variations in the spatial positioning of performers relative to each other in critical performance areas, such as the scoring zones. Implications of this perspective are also considered for practice task design and sport development programmes.

  12. Beam dynamics in disordered P T -symmetric optical lattices based on eigenstate analyses

    NASA Astrophysics Data System (ADS)

    Yao, Xiankun; Liu, Xueming

    2017-03-01

    Wave functions will experience a localization process when evolving in disordered lattices. Here, we have demonstrated the effects of disordered P T -symmetric potentials on wave-function characteristics in optics based on eigenstate analyses. In weak-disorder cases, by using the tight-binding approximation method, a conclusion is obtained that the increasing of the imaginary part of potential can enhance the diffraction, while the increasing disorder will block the diffraction and lead to localization. In the general case, band theory is used for band-structure analysis of three bands. We find that the disorder has a smaller effect on the higher-order band, which is proved by the beam evolutions. Our work may be instructive for realizing beam path control by manipulating the strengths of disorder and gain and/or loss of lattice.

  13. Descriptive and sensitivity analyses of WATBALI: A dynamic soil water model

    NASA Technical Reports Server (NTRS)

    Hildreth, W. W. (Principal Investigator)

    1981-01-01

    A soil water computer model that uses the IBM Continuous System Modeling Program III to solve the dynamic equations representing the soil, plant, and atmospheric physical or physiological processes considered is presented and discussed. Using values describing the soil-plant-atmosphere characteristics, the model predicts evaporation, transpiration, drainage, and soil water profile changes from an initial soil water profile and daily meteorological data. The model characteristics and simulations that were performed to determine the nature of the response to controlled variations in the input are described the results of the simulations are included and a change that makes the response of the model more closely represent the observed characteristics of evapotranspiration and profile changes for dry soil conditions is examined.

  14. Analysing land and vegetation cover dynamics during last three decades in Katerniaghat wildlife sanctuary, India

    NASA Astrophysics Data System (ADS)

    Chitale, V. S.; Behera, M. D.

    2014-10-01

    The change in the tropical forests could be clearly linked to the expansion of the human population and economies. An understanding of the anthropogenic forcing plays an important role in analyzing the impacts of climate change and the fate of tropical forests in the present and future scenario. In the present study, we analyze the impact of natural and anthropogenic factors in forest dynamics in Katerniaghat wildlife sanctuary situated along the Indo-Nepal border in Uttar Pradesh state, India. The study site is under tremendous pressure due to anthropogenic factors from surrounding areas since last three decades. The vegetation cover of the sanctuary primarily comprised of Shorea robusta forests, Tectona grandis plantation, and mixed deciduous forest; while the land cover comprised of agriculture, barren land, and water bodies. The classification accuracy was 83.5%, 91.5%, and 95.2% with MSS, IKONOS, and Quickbird datasets, respectively. Shorea robusta forests showed an increase of 16 km2; while Tectona grandis increased by 63.01 km2 during 1975-2010. The spatial heterogeneity in these tropical vegetation classes surrounded by the human dominated agricultural lands could not be addressed using Landsat MSS data due to coarse spatial resolution; whereas the IKONOS and Quickbird satellite datasets proved to advantageous, thus being able to precisely address the variations within the vegetation classes as well as in the land cover classes and along the edge areas. Massive deforestation during 1970s along the adjoining international boundary with Nepal has led to destruction of the wildlife corridor and has exposed the wildlife sanctuary to human interference like grazing and poaching. Higher rates of forest dynamics during the 25-year period indicate the vulnerability of the ecosystem to the natural and anthropogenic disturbances in the proximity of the sanctuary.

  15. Carotid Artery Stenosis Near a Bifurcation Investigated by Fluid Dynamic Analyses

    PubMed Central

    Filardi, V.

    2013-01-01

    Summary Haemodynamic physical parameters play a role in determining endothelial cell phenotype and influence vascular remodelling. Accurate measurement of total pressure, velocity magnitude, and wall shear stress is vital for studies on the pathogenesis of atherosclerosis. This paper investigated a lesion-based computational fluid dynamic (CFD-Fluent) pilot analysis to understand the complex haemodynamic changes prevailing in patients with high-grade carotid artery stenosis (CS) 90%. All subjects were examined with colour-flow Doppler, power Doppler, and digital subtraction angiography to enable visualization of carotid stenosis and plaque surface morphology, and used to generate computational meshes. Two models were devised: the first without any stenosis and the second with an 82% grade of stenosis localized in the external carotid artery. The distribution of the principal parameters can be obtained by computational fluid dynamics (CFD-Fluent) using patient-specific geometries and flow analytical measurements. The total pressure distribution ranged between 16,000 and 8,000 Pa in the case of normal carotid artery and 16,000 and 5,500 Pa in the case of the stenosed artery. The velocity registered a peak in the stenosis region of 5 m/s. The mean wall shear stress within the stenosis region was 360 Pa. In conclusion, patient-based CFD-Fluent analysis of CS predicts a complex haemodynamic environment with large spatial haemodynamic parameter variations that occur very rapidly over short distances. Our results improve estimates of the flow changes and forces at the vessel wall in CS and the link between haemodynamic changes and stenosis pathophysiology. PMID:24007732

  16. Incorporating Undrained Pore Fuid Pressurization Into Analyses of Off-Fault Plasticity During Dynamic Rupture

    NASA Astrophysics Data System (ADS)

    Viesca, R. C.; Templeton, E. L.; Rice, J. R.

    2007-12-01

    When considering dynamic fault rupture in fluid-saturated elastic-plastic materials, it is sensible to assume locally undrained behavior everywhere except in small diffusive boundary layers along the rupture surface. To evaluate undrained pore pressure changes, we consider here not just the linear poroelastic effect expressed in terms of the Skempton coefficient B, like in our previous work [Viesca et al., AGU Fall 2006], but also include plastic dilatancy, which, when positive, induces a fluid suction. We work in the context of Mohr-Coulomb-like plasticity, but with a Drucker-Prager type model. Plastic parts of strain increments are controlled by the Terzaghi effective stress, elastic parts by the Biot stress combination. Following earlier work of Rudnicki, the incremental elastic-plastic constitutive relation for undrained deformation has precisely the same form as for drained deformation, so long as we change the drained constitutive parameters into new undrained ones under transformation rules that we present. Spontaneous slip-weakening fault rupture is analyzed using the dynamic finite element procedures with ABAQUS Explicit, and undrained elastic-plastic properties. Results are shown for plastic zones and effects on rupture propagation, and how they are influenced by such parameters as B and ratio β of dilatant to shear plastic strains, for a range of principal orientations and magnitudes (relative to yield) of the pre-stress state. The undrained approximation must fail in diffusive boundary layers along the slip surface [Rudnicki and Rice, JGR 2006; Dunham and Rice, AGU Fall 2006] because the predicted pore pressures will be discontinuous at the fault. We show how to extend the Rudnicki and Rice calculation of the actual pore pressure on the fault in terms of the undrained predictions to the two sides. However, because of difficulties thus far in representing this within the ABAQUS program, all results obtained as of the time of writing neglect effects of

  17. dNSP: a biologically inspired dynamic Neural network approach to Signal Processing.

    PubMed

    Cano-Izquierdo, José Manuel; Ibarrola, Julio; Pinzolas, Miguel; Almonacid, Miguel

    2008-09-01

    The arriving order of data is one of the intrinsic properties of a signal. Therefore, techniques dealing with this temporal relation are required for identification and signal processing tasks. To perform a classification of the signal according with its temporal characteristics, it would be useful to find a feature vector in which the temporal attributes were embedded. The correlation and power density spectrum functions are suitable tools to manage this issue. These functions are usually defined with statistical formulation. On the other hand, in biology there can be found numerous processes in which signals are processed to give a feature vector; for example, the processing of sound by the auditory system. In this work, the dNSP (dynamic Neural Signal Processing) architecture is proposed. This architecture allows representing a time-varying signal by a spatial (thus statical) vector. Inspired by the aforementioned biological processes, the dNSP performs frequency decomposition using an analogical parallel algorithm carried out by simple processing units. The architecture has been developed under the paradigm of a multilayer neural network, where the different layers are composed by units whose activation functions have been extracted from the theory of Neural Dynamic [Grossberg, S. (1988). Nonlinear neural networks principles, mechanisms and architectures. Neural Networks, 1, 17-61]. A theoretical study of the behavior of the dynamic equations of the units and their relationship with some statistical functions allows establishing a parallelism between the unit activations and correlation and power density spectrum functions. To test the capabilities of the proposed approach, several testbeds have been employed, i.e. the frequencial study of mathematical functions. As a possible application of the architecture, a highly interesting problem in the field of automatic control is addressed: the recognition of a controlled DC motor operating state.

  18. Quantitative Signaling and Structure-Activity Analyses Demonstrate Functional Selectivity at the Nociceptin/Orphanin FQ Opioid Receptor

    PubMed Central

    Chang, Steven D.; Mascarella, S. Wayne; Spangler, Skylar M.; Gurevich, Vsevolod V.; Navarro, Hernan A.; Carroll, F. Ivy

    2015-01-01

    Comprehensive studies that consolidate selective ligands, quantitative comparisons of G protein versus arrestin-2/3 coupling, together with structure-activity relationship models for G protein–coupled receptor (GPCR) systems are less commonly employed. Here we examine biased signaling at the nociceptin/orphanin FQ opioid receptor (NOPR), the most recently identified member of the opioid receptor family. Using real-time, live-cell assays, we identified the signaling profiles of several NOPR-selective ligands in upstream GPCR signaling (G protein and arrestin pathways) to determine their relative transduction coefficients and signaling bias. Complementing this analysis, we designed novel ligands on the basis of NOPR antagonist J-113,397 [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one] to explore structure-activity relationships. Our study shows that NOPR is capable of biased signaling, and further, the NOPR selective ligands MCOPPB [1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-(3R)-3-piperidinyl-1H-benzimidazole trihydrochloride] and NNC 63-0532 [8-(1-naphthalenylmethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-3-acetic acid, methyl ester] are G protein–biased agonists. Additionally, minor structural modification of J-113,397 can dramatically shift signaling from antagonist to partial agonist activity. We explore these findings with in silico modeling of binding poses. This work is the first to demonstrate functional selectivity and identification of biased ligands at the nociceptin opioid receptor. PMID:26134494

  19. Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics

    PubMed Central

    Friedman, Rachel S.; Beemiller, Peter; Sorensen, Caitlin M.; Jacobelli, Jordan

    2010-01-01

    The real-time dynamics of the T cell receptor (TCR) reflect antigen detection and T cell signaling, providing valuable insight into the evolving events of the immune response. Despite considerable advances in studying TCR dynamics in simplified systems in vitro, live imaging of subcellular signaling complexes expressed at physiological densities in intact tissues has been challenging. In this study, we generated a transgenic mouse with a TCR fused to green fluorescent protein to provide insight into the early signaling events of the immune response. To enable imaging of TCR dynamics in naive T cells in the lymph node, we enhanced signal detection of the fluorescent TCR fusion protein and used volumetric masking with a second fluorophore to mark the T cells expressing the fluorescent TCR. These in vivo analyses and parallel experiments in vitro show minimal and transient incorporation of TCRs into a stable central supramolecular activating cluster (cSMAC) structure but strong evidence for rapid, antigen-dependent TCR internalization that was not contingent on T cell motility arrest or cSMAC formation. Short-lived antigen-independent TCR clustering was also occasionally observed. These in vivo observations demonstrate that varied TCR trafficking and cell arrest dynamics occur during early T cell activation. PMID:21041455

  20. Abstract and Effector-Selective Decision Signals Exhibit Qualitatively Distinct Dynamics before Delayed Perceptual Reports

    PubMed Central

    Twomey, Deirdre M.; Kelly, Simon P.

    2016-01-01

    Electrophysiological research has isolated neural signatures of decision formation in a variety of brain regions. Studies in rodents and monkeys have focused primarily on effector-selective signals that translate the emerging decision into a specific motor plan, but, more recently, research on the human brain has identified an abstract signature of evidence accumulation that does not appear to play any direct role in action preparation. The functional dissociations between these distinct signal types have only begun to be characterized, and their dynamics during decisions with deferred actions with or without foreknowledge of stimulus-effector mapping, a commonly studied task scenario in single-unit and functional imaging investigations, have not been established. Here we traced the dynamics of distinct abstract and effector-selective decision signals in the form of the broad-band centro-parietal positivity (CPP) and limb-selective β-band (8–16 and 18–30 Hz) EEG activity, respectively, during delayed-reported motion direction decisions with and without foreknowledge of direction-response mapping. With foreknowledge, the CPP and β-band signals exhibited a similar gradual build-up following evidence onset, but whereas choice-predictive β-band activity persisted up until the delayed response, the CPP dropped toward baseline after peaking. Without foreknowledge, the CPP exhibited identical dynamics, whereas choice-selective β-band activity was eliminated. These findings highlight qualitative functional distinctions between effector-selective and abstract decision signals and are of relevance to the assumptions founding functional neuroimaging investigations of decision-making. SIGNIFICANCE STATEMENT Neural signatures of evidence accumulation have been isolated in numerous brain regions. Although animal neurophysiology has largely concentrated on effector-selective decision signals that translate the emerging decision into a specific motor plan, recent research

  1. Rosetta lander Philae: Flight Dynamics analyses for landing site selection and post-landing operations

    NASA Astrophysics Data System (ADS)

    Jurado, Eric; Martin, Thierry; Canalias, Elisabet; Blazquez, Alejandro; Garmier, Romain; Ceolin, Thierry; Gaudon, Philippe; Delmas, Cedric; Biele, Jens; Ulamec, Stephan; Remetean, Emile; Torres, Alex; Laurent-Varin, Julien; Dolives, Benoit; Herique, Alain; Rogez, Yves; Kofman, Wlodek; Jorda, Laurent; Zakharov, Vladimir; Crifo, Jean-François; Rodionov, Alexander; Heinish, P.; Vincent, Jean-Baptiste

    2016-08-01

    On the 12th of November 2014, The Rosetta Lander Philae became the first spacecraft to softly land on a comet nucleus. Due to the double failure of the cold gas hold-down thruster and the anchoring harpoons that should have fixed Philae to the surface, it spent approximately two hours bouncing over the comet surface to finally come at rest one km away from its target site. Nevertheless it was operated during the 57 h of its First Science Sequence. The FSS, performed with the two batteries, should have been followed by the Long Term Science Sequence but Philae was in a place not well illuminated and fell into hibernation. Yet, thanks to reducing distance to the Sun and to seasonal effect, it woke up at end of April and on 13th of June it contacted Rosetta again. To achieve this successful landing, an intense preparation work had been carried out mainly between August and November 2014 to select the targeted landing site and define the final landing trajectory. After the landing, the data collected during on-comet operations have been used to assess the final position and orientation of Philae, and to prepare the wake-up. This paper addresses the Flight Dynamics studies done in the scope of this landing preparation from Lander side, in close cooperation with the team at ESA, responsible for Rosetta, as well as for the reconstruction of the bouncing trajectory and orientation of the Lander after touchdown.

  2. Computational Fluid Dynamics Analyses on Very High Temperature Reactor Air Ingress

    SciTech Connect

    Chang H Oh; Eung S. Kim; Richard Schultz; David Petti; Hyung S. Kang

    2009-07-01

    A preliminary computational fluid dynamics (CFD) analysis was performed to understand density-gradient-induced stratified flow in a Very High Temperature Reactor (VHTR) air-ingress accident. Various parameters were taken into consideration, including turbulence model, core temperature, initial air mole-fraction, and flow resistance in the core. The gas turbine modular helium reactor (GT-MHR) 600 MWt was selected as the reference reactor and it was simplified to be 2-D geometry in modeling. The core and the lower plenum were assumed to be porous bodies. Following the preliminary CFD results, the analysis of the air-ingress accident has been performed by two different codes: GAMMA code (system analysis code, Oh et al. 2006) and FLUENT CFD code (Fluent 2007). Eventually, the analysis results showed that the actual onset time of natural convection (~160 sec) would be significantly earlier than the previous predictions (~150 hours) calculated based on the molecular diffusion air-ingress mechanism. This leads to the conclusion that the consequences of this accident will be much more serious than previously expected.

  3. Dynamic path bifurcation in the Beckmann reaction: support from kinetic analyses.

    PubMed

    Yamamoto, Yutaro; Hasegawa, Hiroto; Yamataka, Hiroshi

    2011-06-03

    The reactions of oximes to amides, known as the Beckmann rearrangement, may undergo fragmentation to form carbocations + nitriles when the migrating groups have reasonable stability as cations. The reactions of oxime sulfonates of 1-substituted-phenyl-2-propanone derivatives (7-X) and related substrates (8-X, 9a-X) in aqueous CH(3)CN gave both rearrangement products (amides) and fragmentation products (alcohols), the ratio of which depends on the system; the reactions of 7-X gave amides predominantly, whereas 9a-X yielded alcohols as the major product. The logk-logk plots between the systems gave excellent linear correlations with slopes of near unity. The results support the occurrence of path bifurcation after the rate-determining TS of the Beckmann rearrangement/fragmentation reaction, which has previously been proposed on the basis of molecular dynamics simulations. It was concluded that path-bifurcation phenomenon could be more common than thought and that a reactivity-selectivity argument based on the traditional TS theory may not always be applicable even to a well-known textbook organic reaction.

  4. Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation

    PubMed Central

    Chen, Geng; Schell, John Paul; Benitez, Julio Aguila; Petropoulos, Sophie; Yilmaz, Marlene; Reinius, Björn; Alekseenko, Zhanna; Shi, Leming; Hedlund, Eva; Lanner, Fredrik; Sandberg, Rickard; Deng, Qiaolin

    2016-01-01

    Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we “digitalized” XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI. PMID:27486082

  5. Automated dynamic headspace/GC-MS analyses affect the repeatability of volatiles in irradiated Turkey.

    PubMed

    Nam, Ki-Chang; Cordray, Joseph; Ahn, Dong U

    2004-03-24

    Although a dynamic headspace/gas chromatography-mass spectrometry (DH/GC-MS) method is an effective tool for determining volatiles of irradiated turkey meat, the profile of volatiles may be changeable depending upon the availability of oxygen in the sample vial and sample holding time before purge. The objective of this study was to evaluate the effects of helium flushing and sample holding time before purge on the volatiles profiles of irradiated raw and cooked turkey breast meat. Vacuum-packaged turkey breasts were irradiated at 2.5 kGy, and the volatiles of irradiated raw and cooked samples were analyzed using a DH/GC-MS with different holding times up to 280 min. The amounts of dimethyl disulfide and dimethyl trisulfide decreased as sample holding time in an autosampler (4 degrees C) before purge increased, whereas those of aldehdyes increased as holding time increased due to lipid oxidation. Helium flush of sample vials before sample loading on an autosampler retarded lipid oxidation and minimized the changes of sulfur volatiles in raw meat but was not enough to prevent oxidative changes in cooked meat. Although DH/GC-MS is a convenient method for automatic analysis of volatiles in meat samples, the number of samples that can be loaded in an autosampler at a time should be limited within the range that can permit reasonable repeatabilities for target volatile compounds.

  6. QIN: Practical Considerations in T1 Mapping of Prostate for Dynamic Contrast Enhancement Pharmacokinetic Analyses

    PubMed Central

    Fennessy, Fiona M; Fedorov, Andriy; Gupta, Sandeep N; Schmidt, Ehud J; Tempany, Clare M; Mulkern, Robert V

    2012-01-01

    There are many challenges in developing robust imaging biomarkers that can be reliably applied in a clinical trial setting. In the case of Dynamic Contrast Enhanced (DCE) MRI, one such challenge is to obtain accurate pre-contrast T1 maps for subsequent use in two-compartment pharmacokinetic models commonly used to fit the MR enhancement time courses. In the prostate, a convenient and common approach for this task has been to use the same 3D SPGR sequence used to collect the DCE data, but with variable flip angles (VFA’s) to collect data suitable for T1 mapping prior to contrast injection. However, inhomogeneous radiofrequency conditions within the prostate have been found to adversely affect the accuracy of this technique. Herein we demonstrate the sensitivity of DCE pharmacokinetic parameters to pre-contrast T1 values and examine methods to improve the accuracy of T1 mapping with flip angle corrected VFA SPGR methods, comparing T1 maps from such methods with reference T1 maps generated with saturation recovery experiments performed with fast spin echo (FSE) sequences. PMID:22898681

  7. Detecting dynamic signals of ideally ordered nanohole patterned disk media fabricated using nanoimprint lithography

    NASA Astrophysics Data System (ADS)

    Oshima, Hirotaka; Kikuchi, Hideyuki; Nakao, Hiroshi; Itoh, Ken-ichi; Kamimura, Takuya; Morikawa, Takeshi; Matsumoto, Koji; Umada, Takahiro; Tamura, Hiroaki; Nishio, Kazuyuki; Masuda, Hideki

    2007-07-01

    The authors have fabricated ideally ordered alumina nanohole patterned disk media via anodic oxidation and nanoimprint lithography with a thermoplastic resist. The ordered arrays of alumina nanoholes with 100nm pitch, filled with Co by electrodeposition, were created over a macroscopically large area on a hard-disk substrate using these industrially applicable nanofabrication technologies. Stable flight of a perpendicular magnetic head above the media and perpendicular magnetic anisotropy of the Co nanopillars enable high-speed dynamic magnetic recording and playback. Dynamic periodic signals that matched the nanopillar periodicity were clearly observed after writing bit patterns, showing alternate reversal of magnetization of the nanopillars.

  8. Derivation of soil moisture retrieval uncertainties associated to the simplification of the dynamic vegetation signal.

    NASA Astrophysics Data System (ADS)

    Vreugdenhil, Mariette; Dorigo, Wouter; de Jeu, Richard; Hahn, Sebastian; Salinas, Jose Luis; Wagner, Wolfgang

    2014-05-01

    Satellite-based microwave remote sensing has proven to provide reliable soil moisture observations on a global scale over the last decades. In microwave remote sensing of soil moisture the satellite signal holds information on both soil moisture and vegetation. Separating these components from each other is not straightforward. In the last years the importance of a robust and reliable vegetation parameterization within the soil moisture retrieval algorithms has become evident. In the TU-Wien soil moisture retrieval algorithm, developed by the Vienna University of Technology, the backscatter observations are corrected for vegetation effects by way of the slope and curvature. The slope and curvature are derivates of noisy backscatter measurements in relation to incidence angle and hence have a high level of noise. Therefore, they are averaged over several years resulting in a fixed seasonal vegetation correction, where no inter-annual variability is present in the characterisation of vegetation. This study assesses the strengths and weaknesses of the fixed seasonal vegetation correction in the TU-Wien soil moisture retrieval algorithm. The Vegetation Optical Depth (VOD) retrieved from AMSR-E passive microwave observations with the VUA-NASA retrieval algorithm is analysed to identify regions with high inter-annual variability in vegetation. For these regions the effect of a fixed seasonal correction on the soil moisture retrieval is investigated. First, the TU-Wien soil moisture products before and after the application of the vegetation correction, the TU-Wien normalised backscatter and TU-Wien soil moisture respectively, are compared to modelled soil moisture from ECMWFs ERA-Interim. With this analysis regions where the vegetation correction decreases the quality of the TU-Wien soil moisture product with regard to modeled soil moisture can be identified. Secondly, the vegetation correction within the TU-Wien retrieval algorithm is replaced by the VOD to simulate an

  9. A comparative study of cold- and warm-adapted Endonucleases A using sequence analyses and molecular dynamics simulations.

    PubMed

    Michetti, Davide; Brandsdal, Bjørn Olav; Bon, Davide; Isaksen, Geir Villy; Tiberti, Matteo; Papaleo, Elena

    2017-01-01

    The psychrophilic and mesophilic endonucleases A (EndA) from Aliivibrio salmonicida (VsEndA) and Vibrio cholera (VcEndA) have been studied experimentally in terms of the biophysical properties related to thermal adaptation. The analyses of their static X-ray structures was no sufficient to rationalize the determinants of their adaptive traits at the molecular level. Thus, we used Molecular Dynamics (MD) simulations to compare the two proteins and unveil their structural and dynamical differences. Our simulations did not show a substantial increase in flexibility in the cold-adapted variant on the nanosecond time scale. The only exception is a more rigid C-terminal region in VcEndA, which is ascribable to a cluster of electrostatic interactions and hydrogen bonds, as also supported by MD simulations of the VsEndA mutant variant where the cluster of interactions was introduced. Moreover, we identified three additional amino acidic substitutions through multiple sequence alignment and the analyses of MD-based protein structure networks. In particular, T120V occurs in the proximity of the catalytic residue H80 and alters the interaction with the residue Y43, which belongs to the second coordination sphere of the Mg2+ ion. This makes T120V an amenable candidate for future experimental mutagenesis.

  10. Dynamic optical interferometry applied to analyse out of plane displacement fields for crack propagation in brittle materials

    NASA Astrophysics Data System (ADS)

    Hedan, S.; Pop, O.; Valle, V.; Cottron, M.

    2006-08-01

    We propose in this paper, to analyse, the evolution of out-of-plane displacement fields for a crack propagation in brittle materials. As the crack propagation is a complex process that involves the deformation mechanisms, the out-of-plane displacement measurement gives pertinent information about the 3D effects. For investigation, we use the interferometric method. The optical device includes a laser source, a Michelson interferometer and an ultra high-speed CCD camera. To take into account the crack velocity, we dispose of a maximum frame rate of 1Mfps. The experimental tests have been carried out for a SEN (Single Edge Notch) specimen of PMMA material. The crack propagation is initiated by adding a dynamic energy given by the impact of a cutter on the initial crack. The obtained interferograms are analysed with a new phase extraction method entitled MPC [6]. This analysis, which has been developed specially for dynamic studies, gives the out-of-plane displacement with an accuracy of about 10 nm.

  11. On protection of Freedom's solar dynamic radiator from the orbital debris environment. Part 1: Preliminary analyses and testing

    NASA Technical Reports Server (NTRS)

    Rhatigan, Jennifer L.; Christiansen, Eric L.; Fleming, Michael L.

    1990-01-01

    A great deal of experimentation and analysis was performed to quantify penetration thresholds of components which will experience orbital debris impacts. Penetration was found to depend upon mission specific parameters such as orbital altitude, inclination, and orientation of the component; and upon component specific parameters such as material, density and the geometry particular to its shielding. Experimental results are highly dependent upon shield configuration and cannot be extrapolated with confidence to alternate shield configurations. Also, current experimental capabilities are limited to velocities which only approach the lower limit of predicted orbital debris velocities. Therefore, prediction of the penetrating particle size for a particular component having a complex geometry remains highly uncertain. An approach is described which was developed to assess on-orbit survivability of the solar dynamic radiator due to micrometeoroid and space debris impacts. Preliminary analyses are presented to quantify the solar dynamic radiator survivability, and include the type of particle and particle population expected to defeat the radiator bumpering (i.e., penetrate a fluid flow tube). Results of preliminary hypervelocity impact testing performed on radiator panel samples (in the 6 to 7 km/sec velocity range) are also presented. Plans for further analyses and testing are discussed. These efforts are expected to lead to a radiator design which will perform to requirements over the expected lifetime.

  12. On protection of Freedom's solar dynamic radiator from the orbital debris environment. Part 1. Preliminary analyses and testing

    SciTech Connect

    Rhatigan, J.L.; Christiansen, E.L.; Fleming, M.L.

    1990-01-01

    A great deal of experimentation and analysis was performed to quantify penetration thresholds of components which will experience orbital debris impacts. Penetration was found to depend upon mission specific parameters such as orbital altitude, inclination, and orientation of the component; and upon component specific parameters such as material, density and the geometry particular to its shielding. Experimental results are highly dependent upon shield configuration and cannot be extrapolated with confidence to alternate shield configurations. Also, current experimental capabilities are limited to velocities which only approach the lower limit of predicted orbital debris velocities. Therefore, prediction of the penetrating particle size for a particular component having a complex geometry remains highly uncertain. An approach is described which was developed to assess on-orbit survivability of the solar dynamic radiator due to micrometeoroid and space debris impacts. Preliminary analyses are presented to quantify the solar dynamic radiator survivability, and include the type of particle and particle population expected to defeat the radiator bumpering (i.e., penetrate a fluid flow tube). Results of preliminary hypervelocity impact testing performed on radiator panel samples (in the 6 to 7 km/sec velocity range) are also presented. Plans for further analyses and testing are discussed. These efforts are expected to lead to a radiator design which will perform to requirements over the expected lifetime.

  13. A comparative study of cold- and warm-adapted Endonucleases A using sequence analyses and molecular dynamics simulations

    PubMed Central

    Michetti, Davide; Brandsdal, Bjørn Olav; Bon, Davide; Isaksen, Geir Villy; Tiberti, Matteo; Papaleo, Elena

    2017-01-01

    The psychrophilic and mesophilic endonucleases A (EndA) from Aliivibrio salmonicida (VsEndA) and Vibrio cholera (VcEndA) have been studied experimentally in terms of the biophysical properties related to thermal adaptation. The analyses of their static X-ray structures was no sufficient to rationalize the determinants of their adaptive traits at the molecular level. Thus, we used Molecular Dynamics (MD) simulations to compare the two proteins and unveil their structural and dynamical differences. Our simulations did not show a substantial increase in flexibility in the cold-adapted variant on the nanosecond time scale. The only exception is a more rigid C-terminal region in VcEndA, which is ascribable to a cluster of electrostatic interactions and hydrogen bonds, as also supported by MD simulations of the VsEndA mutant variant where the cluster of interactions was introduced. Moreover, we identified three additional amino acidic substitutions through multiple sequence alignment and the analyses of MD-based protein structure networks. In particular, T120V occurs in the proximity of the catalytic residue H80 and alters the interaction with the residue Y43, which belongs to the second coordination sphere of the Mg2+ ion. This makes T120V an amenable candidate for future experimental mutagenesis. PMID:28192428

  14. Phylogenetic and Metagenomic Analyses of Substrate-Dependent Bacterial Temporal Dynamics in Microbial Fuel Cells

    PubMed Central

    Zhang, Husen; Chen, Xi; Braithwaite, Daniel; He, Zhen

    2014-01-01

    Understanding the microbial community structure and genetic potential of anode biofilms is key to improve extracellular electron transfers in microbial fuel cells. We investigated effect of substrate and temporal dynamics of anodic biofilm communities using phylogenetic and metagenomic approaches in parallel with electrochemical characterizations. The startup non-steady state anodic bacterial structures were compared for a simple substrate, acetate, and for a complex substrate, landfill leachate, using a single-chamber air-cathode microbial fuel cell. Principal coordinate analysis showed that distinct community structures were formed with each substrate type. The bacterial diversity measured as Shannon index decreased with time in acetate cycles, and was restored with the introduction of leachate. The change of diversity was accompanied by an opposite trend in the relative abundance of Geobacter-affiliated phylotypes, which were acclimated to over 40% of total Bacteria at the end of acetate-fed conditions then declined in the leachate cycles. The transition from acetate to leachate caused a decrease in output power density from 243±13 mW/m2 to 140±11 mW/m2, accompanied by a decrease in Coulombic electron recovery from 18±3% to 9±3%. The leachate cycles selected protein-degrading phylotypes within phylum Synergistetes. Metagenomic shotgun sequencing showed that leachate-fed communities had higher cell motility genes including bacterial chemotaxis and flagellar assembly, and increased gene abundance related to metal resistance, antibiotic resistance, and quorum sensing. These differentially represented genes suggested an altered anodic biofilm community in response to additional substrates and stress from the complex landfill leachate. PMID:25202990

  15. A New Concurrent Multiscale Methodology for Coupling Molecular Dynamics and Finite Element Analyses

    NASA Technical Reports Server (NTRS)

    Yamakov, Vesselin; Saether, Erik; Glaessgen, Edward H/.

    2008-01-01

    The coupling of molecular dynamics (MD) simulations with finite element methods (FEM) yields computationally efficient models that link fundamental material processes at the atomistic level with continuum field responses at higher length scales. The theoretical challenge involves developing a seamless connection along an interface between two inherently different simulation frameworks. Various specialized methods have been developed to solve particular classes of problems. Many of these methods link the kinematics of individual MD atoms with FEM nodes at their common interface, necessarily requiring that the finite element mesh be refined to atomic resolution. Some of these coupling approaches also require simulations to be carried out at 0 K and restrict modeling to two-dimensional material domains due to difficulties in simulating full three-dimensional material processes. In the present work, a new approach to MD-FEM coupling is developed based on a restatement of the standard boundary value problem used to define a coupled domain. The method replaces a direct linkage of individual MD atoms and finite element (FE) nodes with a statistical averaging of atomistic displacements in local atomic volumes associated with each FE node in an interface region. The FEM and MD computational systems are effectively independent and communicate only through an iterative update of their boundary conditions. With the use of statistical averages of the atomistic quantities to couple the two computational schemes, the developed approach is referred to as an embedded statistical coupling method (ESCM). ESCM provides an enhanced coupling methodology that is inherently applicable to three-dimensional domains, avoids discretization of the continuum model to atomic scale resolution, and permits finite temperature states to be applied.

  16. An Embedded Statistical Method for Coupling Molecular Dynamics and Finite Element Analyses

    NASA Technical Reports Server (NTRS)

    Saether, E.; Glaessgen, E.H.; Yamakov, V.

    2008-01-01

    The coupling of molecular dynamics (MD) simulations with finite element methods (FEM) yields computationally efficient models that link fundamental material processes at the atomistic level with continuum field responses at higher length scales. The theoretical challenge involves developing a seamless connection along an interface between two inherently different simulation frameworks. Various specialized methods have been developed to solve particular classes of problems. Many of these methods link the kinematics of individual MD atoms with FEM nodes at their common interface, necessarily requiring that the finite element mesh be refined to atomic resolution. Some of these coupling approaches also require simulations to be carried out at 0 K and restrict modeling to two-dimensional material domains due to difficulties in simulating full three-dimensional material processes. In the present work, a new approach to MD-FEM coupling is developed based on a restatement of the standard boundary value problem used to define a coupled domain. The method replaces a direct linkage of individual MD atoms and finite element (FE) nodes with a statistical averaging of atomistic displacements in local atomic volumes associated with each FE node in an interface region. The FEM and MD computational systems are effectively independent and communicate only through an iterative update of their boundary conditions. With the use of statistical averages of the atomistic quantities to couple the two computational schemes, the developed approach is referred to as an embedded statistical coupling method (ESCM). ESCM provides an enhanced coupling methodology that is inherently applicable to three-dimensional domains, avoids discretization of the continuum model to atomic scale resolution, and permits finite temperature states to be applied.

  17. Dynamic characteristics of laser Doppler flowmetry signals obtained in response to a local and progressive pressure applied on diabetic and healthy subjects

    NASA Astrophysics Data System (ADS)

    Humeau, Anne; Koitka, Audrey; Abraham, Pierre; Saumet, Jean-Louis; L'Huillier, Jean-Pierre

    2004-09-01

    In the biomedical field, the laser Doppler flowmetry (LDF) technique is a non-invasive method to monitor skin perfusion. On the skin of healthy humans, LDF signals present a significant transient increase in response to a local and progressive pressure application. This vasodilatory reflex response may have important implications for cutaneous pathologies involved in various neurological diseases and in the pathophysiology of decubitus ulcers. The present work analyses the dynamic characteristics of these signals on young type 1 diabetic patients, and on healthy age-matched subjects. To obtain accurate dynamic characteristic values, a de-noising wavelet-based algorithm is first applied to LDF signals. All the de-noised signals are then normalised to the same value. The blood flow peak and the time to reach this peak are then calculated on each computed signal. The results show that a large vasodilation is present on signals of healthy subjects. The mean peak occurs at a pressure of 3.2 kPa approximately. However, a vasodilation of limited amplitude appears on type 1 diabetic patients. The maximum value is visualised, on the average, when the pressure is 1.1 kPa. The inability for diabetic patients to increase largely their cutaneous blood flow may bring explanations to foot ulcers.

  18. Cell signaling and mitochondrial dynamics: implications for neuronal function and neurodegenerative disease

    PubMed Central

    Wilson, Theodore J.; Slupe, Andrew M.; Strack, Stefan

    2012-01-01

    Nascent evidence indicates that mitochondrial fission, fusion, and transport are subject to intricate regulatory mechanisms that intersect with both well-characterized and emerging signaling pathways. While it is well established that mutations in components of the mitochondrial fission/fusion machinery can cause neurological disorders, relatively little is known about upstream regulators of mitochondrial dynamics and their role in neurodegeneration. Here, we review posttranslational regulation of mitochondrial fission/fusion enzymes, with particular emphasis on dynamin-related protein 1 (Drp1), as well as outer mitochondrial signaling complexes involving protein kinases and phosphatases. We also review recent evidence that mitochondrial dynamics has profound consequences for neuronal development and synaptic transmission and discuss implications for clinical translation. PMID:22297163

  19. Spacecraft attitude control systems with dynamic methods and structures for processing star tracker signals

    NASA Technical Reports Server (NTRS)

    Liu, Yong (Inventor); Wu, Yeong-Wei Andy (Inventor); Li, Rongsheng (Inventor)

    2001-01-01

    Methods are provided for dynamically processing successively-generated star tracker data frames and associated valid flags to generate processed star tracker signals that have reduced noise and a probability greater than a selected probability P.sub.slctd of being valid. These methods maintain accurate spacecraft attitude control in the presence of spurious inputs (e.g., impinging protons) that corrupt collected charges in spacecraft star trackers. The methods of the invention enhance the probability of generating valid star tracker signals because they respond to a current frame probability P.sub.frm by dynamically selecting the largest valid frame combination whose combination probability P.sub.cmb satisfies a selected probability P.sub.slctd. Noise is thus reduced while the probability of finding a valid frame combination is enhanced. Spacecraft structures are also provided for practicing the methods of the invention.

  20. Adaptive coded spreading OFDM signal for dynamic-λ optical access network

    NASA Astrophysics Data System (ADS)

    Liu, Bo; Zhang, Lijia; Xin, Xiangjun

    2015-12-01

    This paper proposes and experimentally demonstrates a novel adaptive coded spreading (ACS) orthogonal frequency division multiplexing (OFDM) signal for dynamic distributed optical ring-based access network. The wavelength can be assigned to different remote nodes (RNs) according to the traffic demand of optical network unit (ONU). The ACS can provide dynamic spreading gain to different signals according to the split ratio or transmission length, which offers flexible power budget for the network. A 10×13.12 Gb/s OFDM access with ACS is successfully demonstrated over two RNs and 120 km transmission in the experiment. The demonstrated method may be viewed as one promising for future optical metro access network.

  1. Digital signal processing for velocity measurements in dynamical material's behaviour studies.

    PubMed

    Devlaminck, Julien; Luc, Jérôme; Chanal, Pierre-Yves

    2014-03-01

    In this work, we describe different configurations of optical fiber interferometers (types Michelson and Mach-Zehnder) used to measure velocities during dynamical material's behaviour studies. We detail the algorithms of processing developed and optimized to improve the performance of these interferometers especially in terms of time and frequency resolutions. Three methods of analysis of interferometric signals were studied. For Michelson interferometers, the time-frequency analysis of signals by Short-Time Fourier Transform (STFT) is compared to a time-frequency analysis by Continuous Wavelet Transform (CWT). The results have shown that the CWT was more suitable than the STFT for signals with low signal-to-noise, and low velocity and high acceleration areas. For Mach-Zehnder interferometers, the measurement is carried out by analyzing the phase shift between three interferometric signals (Triature processing). These three methods of digital signal processing were evaluated, their measurement uncertainties estimated, and their restrictions or operational limitations specified from experimental results performed on a pulsed power machine.

  2. Digital signal processing for velocity measurements in dynamical material's behaviour studies

    NASA Astrophysics Data System (ADS)

    Devlaminck, Julien; Luc, Jérôme; Chanal, Pierre-Yves

    2014-03-01

    In this work, we describe different configurations of optical fiber interferometers (types Michelson and Mach-Zehnder) used to measure velocities during dynamical material's behaviour studies. We detail the algorithms of processing developed and optimized to improve the performance of these interferometers especially in terms of time and frequency resolutions. Three methods of analysis of interferometric signals were studied. For Michelson interferometers, the time-frequency analysis of signals by Short-Time Fourier Transform (STFT) is compared to a time-frequency analysis by Continuous Wavelet Transform (CWT). The results have shown that the CWT was more suitable than the STFT for signals with low signal-to-noise, and low velocity and high acceleration areas. For Mach-Zehnder interferometers, the measurement is carried out by analyzing the phase shift between three interferometric signals (Triature processing). These three methods of digital signal processing were evaluated, their measurement uncertainties estimated, and their restrictions or operational limitations specified from experimental results performed on a pulsed power machine.

  3. Genetically encoded molecular probes to visualize and perturb signaling dynamics in living biological systems

    PubMed Central

    Sample, Vedangi; Mehta, Sohum; Zhang, Jin

    2014-01-01

    ABSTRACT In this Commentary, we discuss two sets of genetically encoded molecular tools that have significantly enhanced our ability to observe and manipulate complex biochemical processes in their native context and that have been essential in deepening our molecular understanding of how intracellular signaling networks function. In particular, genetically encoded biosensors are widely used to directly visualize signaling events in living cells, and we highlight several examples of basic biosensor designs that have enabled researchers to capture the spatial and temporal dynamics of numerous signaling molecules, including second messengers and signaling enzymes, with remarkable detail. Similarly, we discuss a number of genetically encoded biochemical perturbation techniques that are being used to manipulate the activity of various signaling molecules with far greater spatial and temporal selectivity than can be achieved using standard pharmacological or genetic techniques, focusing specifically on examples of chemically driven and light-inducible perturbation strategies. We then describe recent efforts to combine these diverse and powerful molecular tools into a unified platform that can be used to elucidate the molecular details of biological processes that may potentially extend well beyond the realm of signal transduction. PMID:24634506

  4. Daniel K. Inouye Solar Telescope: computational fluid dynamic analyses and evaluation of the air knife model

    NASA Astrophysics Data System (ADS)

    McQuillen, Isaac; Phelps, LeEllen; Warner, Mark; Hubbard, Robert

    2016-08-01

    Implementation of an air curtain at the thermal boundary between conditioned and ambient spaces allows for observation over wavelength ranges not practical when using optical glass as a window. The air knife model of the Daniel K. Inouye Solar Telescope (DKIST) project, a 4-meter solar observatory that will be built on Haleakalā, Hawai'i, deploys such an air curtain while also supplying ventilation through the ceiling of the coudé laboratory. The findings of computational fluid dynamics (CFD) analysis and subsequent changes to the air knife model are presented. Major design constraints include adherence to the Interface Control Document (ICD), separation of ambient and conditioned air, unidirectional outflow into the coudé laboratory, integration of a deployable glass window, and maintenance and accessibility requirements. Optimized design of the air knife successfully holds full 12 Pa backpressure under temperature gradients of up to 20°C while maintaining unidirectional outflow. This is a significant improvement upon the .25 Pa pressure differential that the initial configuration, tested by Linden and Phelps, indicated the curtain could hold. CFD post- processing, developed by Vogiatzis, is validated against interferometry results of initial air knife seeing evaluation, performed by Hubbard and Schoening. This is done by developing a CFD simulation of the initial experiment and using Vogiatzis' method to calculate error introduced along the optical path. Seeing error, for both temperature differentials tested in the initial experiment, match well with seeing results obtained from the CFD analysis and thus validate the post-processing model. Application of this model to the realizable air knife assembly yields seeing errors that are well within the error budget under which the air knife interface falls, even with a temperature differential of 20°C between laboratory and ambient spaces. With ambient temperature set to 0°C and conditioned temperature set to 20

  5. Effect of Nasal Obstruction on Continuous Positive Airway Pressure Treatment: Computational Fluid Dynamics Analyses

    PubMed Central

    Wakayama, Tadashi; Suzuki, Masaaki; Tanuma, Tadashi

    2016-01-01

    Objective Nasal obstruction is a common problem in continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea and limits treatment compliance. The purpose of this study is to model the effects of nasal obstruction on airflow parameters under CPAP using computational fluid dynamics (CFD), and to clarify quantitatively the relation between airflow velocity and pressure loss coefficient in subjects with and without nasal obstruction. Methods We conducted an observational cross-sectional study of 16 Japanese adult subjects, of whom 9 had nasal obstruction and 7 did not (control group). Three-dimensional reconstructed models of the nasal cavity and nasopharynx with a CPAP mask fitted to the nostrils were created from each subject’s CT scans. The digital models were meshed with tetrahedral cells and stereolithography formats were created. CPAP airflow simulations were conducted using CFD software. Airflow streamlines and velocity contours in the nasal cavities and nasopharynx were compared between groups. Simulation models were confirmed to agree with actual measurements of nasal flow rate and with pressure and flow rate in the CPAP machine. Results Under 10 cmH2O CPAP, average maximum airflow velocity during inspiration was 17.6 ± 5.6 m/s in the nasal obstruction group but only 11.8 ± 1.4 m/s in the control group. The average pressure drop in the nasopharynx relative to inlet static pressure was 2.44 ± 1.41 cmH2O in the nasal obstruction group but only 1.17 ± 0.29 cmH2O in the control group. The nasal obstruction and control groups were clearly separated by a velocity threshold of 13.5 m/s, and pressure loss coefficient threshold of approximately 10.0. In contrast, there was no significant difference in expiratory pressure in the nasopharynx between the groups. Conclusion This is the first CFD analysis of the effect of nasal obstruction on CPAP treatment. A strong correlation between the inspiratory pressure loss coefficient and maximum airflow

  6. Human-arm-and-hand-dynamic model with variability analyses for a stylus-based haptic interface.

    PubMed

    Fu, Michael J; Cavuşoğlu, M Cenk

    2012-12-01

    Haptic interface research benefits from accurate human arm models for control and system design. The literature contains many human arm dynamic models but lacks detailed variability analyses. Without accurate measurements, variability is modeled in a very conservative manner, leading to less than optimal controller and system designs. This paper not only presents models for human arm dynamics but also develops inter- and intrasubject variability models for a stylus-based haptic device. Data from 15 human subjects (nine male, six female, ages 20-32) were collected using a Phantom Premium 1.5a haptic device for system identification. In this paper, grip-force-dependent models were identified for 1-3-N grip forces in the three spatial axes. Also, variability due to human subjects and grip-force variation were modeled as both structured and unstructured uncertainties. For both forms of variability, the maximum variation, 95 %, and 67 % confidence interval limits were examined. All models were in the frequency domain with force as input and position as output. The identified models enable precise controllers targeted to a subset of possible human operator dynamics.

  7. Individual-Environment Interactions in Swimming: The Smallest Unit for Analysing the Emergence of Coordination Dynamics in Performance?

    PubMed

    Guignard, Brice; Rouard, Annie; Chollet, Didier; Hart, John; Davids, Keith; Seifert, Ludovic

    2017-02-08

    Displacement in competitive swimming is highly dependent on fluid characteristics, since athletes use these properties to propel themselves. It is essential for sport scientists and practitioners to clearly identify the interactions that emerge between each individual swimmer and properties of an aquatic environment. Traditionally, the two protagonists in these interactions have been studied separately. Determining the impact of each swimmer's movements on fluid flow, and vice versa, is a major challenge. Classic biomechanical research approaches have focused on swimmers' actions, decomposing stroke characteristics for analysis, without exploring perturbations to fluid flows. Conversely, fluid mechanics research has sought to record fluid behaviours, isolated from the constraints of competitive swimming environments (e.g. analyses in two-dimensions, fluid flows passively studied on mannequins or robot effectors). With improvements in technology, however, recent investigations have focused on the emergent circular couplings between swimmers' movements and fluid dynamics. Here, we provide insights into concepts and tools that can explain these on-going dynamic interactions in competitive swimming within the theoretical framework of ecological dynamics.

  8. Novel optical-based methods and analyses for elucidating cellular mechanics and dynamics

    NASA Astrophysics Data System (ADS)

    Koo, Peter K.

    Resolving distinct biochemical interaction states by analyzing the diffusive behaviors of individual protein trajectories is challenging due to the limited statistics provided by short trajectories and experimental noise sources, which are intimately coupled into each proteins localization. In the first part of this thesis, we introduce a novel, a machine-learning based classification methodology, called perturbation expectation-maximization (pEM), which simultaneously analyzes a population of protein trajectories to uncover the system of short-time diffusive behaviors which collectively result from distinct biochemical interactions. We then discuss an experimental application of pEM to Rho GTPase, an integral regulator of cytoskeletal dynamics and cellular homeostasis, inside live cells. We also derive the maximum likelihood estimator (MLE) for driven diffusion, confined diffusion, and fractional Brownian motion. We demonstrate that MLE yields improved estimates in comparison with traditional diffusion analysis, namely mean squared displacement analysis. In addition, we also introduce mleBayes, which is an empirical Bayesian model selection scheme to classify an individual protein trajectory to a given diffusion mode. By employing mleBayes on simulated data, we demonstrate that accurate determination of the underlying diffusive properties, beyond normal diffusion, remains challenging when analyzing particle trajectories on an individual basis. To improve upon the statistical limitations of classification from analyzing trajectories on an individual basis, we extend pEM with a new version (pEMv2) to simultaneously analyzing a collection of particle trajectories to uncover the system of interactions which give rise to unique normal or non-normal diffusive states. We test the performance of pEMv2 on various sets of simulated particle trajectories which transition between various modes of normal and non-normal diffusive states to highlight considerations when

  9. Identifying early-warning signals of critical transitions with strong noise by dynamical network markers.

    PubMed

    Liu, Rui; Chen, Pei; Aihara, Kazuyuki; Chen, Luonan

    2015-12-09

    Identifying early-warning signals of a critical transition for a complex system is difficult, especially when the target system is constantly perturbed by big noise, which makes the traditional methods fail due to the strong fluctuations of the observed data. In this work, we show that the critical transition is not traditional state-transition but probability distribution-transition when the noise is not sufficiently small, which, however, is a ubiquitous case in real systems. We present a model-free computational method to detect the warning signals before such transitions. The key idea behind is a strategy: "making big noise smaller" by a distribution-embedding scheme, which transforms the data from the observed state-variables with big noise to their distribution-variables with small noise, and thus makes the traditional criteria effective because of the significantly reduced fluctuations. Specifically, increasing the dimension of the observed data by moment expansion that changes the system from state-dynamics to probability distribution-dynamics, we derive new data in a higher-dimensional space but with much smaller noise. Then, we develop a criterion based on the dynamical network marker (DNM) to signal the impending critical transition using the transformed higher-dimensional data. We also demonstrate the effectiveness of our method in biological, ecological and financial systems.

  10. Weak and Dynamic GNSS Signal Tracking Strategies for Flight Missions in the Space Service Volume.

    PubMed

    Jing, Shuai; Zhan, Xingqun; Liu, Baoyu; Chen, Maolin

    2016-09-02

    Weak-signal and high-dynamics are of two primary concerns of space navigation using GNSS (Global Navigation Satellite System) in the space service volume (SSV). The paper firstly defines a reference assumption third-order phase-locked loop (PLL) as the baseline of an onboard GNSS receiver, and proves the incompetence of this conventional architecture. Then an adaptive four-state Kalman filter (KF)-based algorithm is introduced to realize the optimization of loop noise bandwidth, which can adaptively regulate its filter gain according to the received signal power and line-of-sight (LOS) dynamics. To overcome the matter of losing lock in weak-signal and high-dynamic environments, an open loop tracking strategy aided by an inertial navigation system (INS) is recommended, and the traditional maximum likelihood estimation (MLE) method is modified in a non-coherent way by reconstructing the likelihood cost function. Furthermore, a typical mission with combined orbital maneuvering and non-maneuvering arcs is taken as a destination object to test the two proposed strategies. Finally, the experiment based on computer simulation identifies the effectiveness of an adaptive four-state KF-based strategy under non-maneuvering conditions and the virtue of INS-assisted methods under maneuvering conditions.

  11. Exploration of trade-offs between steady-state and dynamic properties in signaling cycles

    NASA Astrophysics Data System (ADS)

    Radivojevic, A.; Chachuat, B.; Bonvin, D.; Hatzimanikatis, V.

    2012-08-01

    In the intracellular signaling networks that regulate important cell processes, the base pattern comprises the cycle of reversible phosphorylation of a protein, catalyzed by kinases and opposing phosphatases. Mathematical modeling and analysis have been used for gaining a better understanding of their functions and to capture the rules governing system behavior. Since biochemical parameters in signaling pathways are not easily accessible experimentally, it is necessary to explore possibilities for both steady-state and dynamic responses in these systems. While a number of studies have focused on analyzing these properties separately, it is necessary to take into account both of these responses simultaneously in order to be able to interpret a broader range of phenotypes. This paper investigates the trade-offs between optimal characteristics of both steady-state and dynamic responses. Following an inverse sensitivity analysis approach, we use systematic optimization methods to find the biochemical and biophysical parameters that simultaneously achieve optimal steady-state and dynamic performance. Remarkably, we find that even a single covalent modification cycle can simultaneously and robustly achieve high ultrasensitivity, high amplification and rapid signal transduction. We also find that the response rise and decay times can be modulated independently by varying the activating- and deactivating-enzyme-to-interconvertible-protein ratios.

  12. Digital-signal-processor-based dynamic imaging system for optical tomography.

    PubMed

    Lasker, Joseph M; Masciotti, James M; Schoenecker, Matthew; Schmitz, Christoph H; Hielscher, Andreas H

    2007-08-01

    In this article, we introduce a dynamic optical tomography system that is, unlike currently available analog instrumentation, based on digital data acquisition and filtering techniques. At the core of this continuous wave instrument is a digital signal processor (DSP) that collects, collates, processes, and filters the digitized data set. The processor is also responsible for managing system timing and the imaging routines which can acquire real-time data at rates as high as 150 Hz. Many of the synchronously timed processes are controlled by a complex programmable logic device that is also used in conjunction with the DSP to orchestrate data flow. The operation of the system is implemented through a comprehensive graphical user interface designed with LABVIEW software which integrates automated calibration, data acquisition, data organization, and signal postprocessing. Performance analysis demonstrates very low system noise (approximately 1 pW rms noise equivalent power), excellent signal precision (<0.04%-0.2%) and long term system stability (<1% over 40 min). A large dynamic range (approximately 190 dB) accommodates a wide scope of measurement geometries and tissue types. First experiments on tissue phantoms show that dynamic behavior is accurately captured and spatial location can be correctly tracked using this system.

  13. High-throughput microfluidics to control and measure signaling dynamics in single yeast cells

    PubMed Central

    Hansen, Anders S.; Hao, Nan; O'Shea, Erin K.

    2015-01-01

    Microfluidics coupled to quantitative time-lapse fluorescence microscopy is transforming our ability to control, measure, and understand signaling dynamics in single living cells. Here we describe a pipeline that incorporates multiplexed microfluidic cell culture, automated programmable fluid handling for cell perturbation, quantitative time-lapse microscopy, and computational analysis of time-lapse movies. We illustrate how this setup can be used to control the nuclear localization of the budding yeast transcription factor Msn2. Using this protocol, we generate oscillations of Msn2 localization and measure the dynamic gene expression response of individual genes in single cells. The protocol allows a single researcher to perform up to 20 different experiments in a single day, whilst collecting data for thousands of single cells. Compared to other protocols, the present protocol is relatively easy to adopt and higher-throughput. The protocol can be widely used to control and monitor single-cell signaling dynamics in other signal transduction systems in microorganisms. PMID:26158443

  14. Identifying early-warning signals of critical transitions with strong noise by dynamical network markers

    PubMed Central

    Liu, Rui; Chen, Pei; Aihara, Kazuyuki; Chen, Luonan

    2015-01-01

    Identifying early-warning signals of a critical transition for a complex system is difficult, especially when the target system is constantly perturbed by big noise, which makes the traditional methods fail due to the strong fluctuations of the observed data. In this work, we show that the critical transition is not traditional state-transition but probability distribution-transition when the noise is not sufficiently small, which, however, is a ubiquitous case in real systems. We present a model-free computational method to detect the warning signals before such transitions. The key idea behind is a strategy: “making big noise smaller” by a distribution-embedding scheme, which transforms the data from the observed state-variables with big noise to their distribution-variables with small noise, and thus makes the traditional criteria effective because of the significantly reduced fluctuations. Specifically, increasing the dimension of the observed data by moment expansion that changes the system from state-dynamics to probability distribution-dynamics, we derive new data in a higher-dimensional space but with much smaller noise. Then, we develop a criterion based on the dynamical network marker (DNM) to signal the impending critical transition using the transformed higher-dimensional data. We also demonstrate the effectiveness of our method in biological, ecological and financial systems. PMID:26647650

  15. Weak temporal signals can synchronize and accelerate the transition dynamics of biopolymers under tension.

    PubMed

    Kim, Won Kyu; Hyeon, Changbong; Sung, Wokyung

    2012-09-04

    In addition to thermal noise, which is essential to promote conformational transitions in biopolymers, the cellular environment is replete with a spectrum of athermal fluctuations that are produced from a plethora of active processes. To understand the effect of athermal noise on biological processes, we studied how a small oscillatory force affects the thermally induced folding and unfolding transition of an RNA hairpin, whose response to constant tension had been investigated extensively in both theory and experiments. Strikingly, our molecular simulations performed under overdamped condition show that even at a high (low) tension that renders the hairpin (un)folding improbable, a weak external oscillatory force at a certain frequency can synchronously enhance the transition dynamics of RNA hairpin and increase the mean transition rate. Furthermore, the RNA dynamics can still discriminate a signal with resonance frequency even when the signal is mixed among other signals with nonresonant frequencies. In fact, our computational demonstration of thermally induced resonance in RNA hairpin dynamics is a direct realization of the phenomena called stochastic resonance and resonant activation. Our study, amenable to experimental tests using optical tweezers, is of great significance to the folding of biopolymers in vivo that are subject to the broad spectrum of cellular noises.

  16. Identifying early-warning signals of critical transitions with strong noise by dynamical network markers

    NASA Astrophysics Data System (ADS)

    Liu, Rui; Chen, Pei; Aihara, Kazuyuki; Chen, Luonan

    2015-12-01

    Identifying early-warning signals of a critical transition for a complex system is difficult, especially when the target system is constantly perturbed by big noise, which makes the traditional methods fail due to the strong fluctuations of the observed data. In this work, we show that the critical transition is not traditional state-transition but probability distribution-transition when the noise is not sufficiently small, which, however, is a ubiquitous case in real systems. We present a model-free computational method to detect the warning signals before such transitions. The key idea behind is a strategy: “making big noise smaller” by a distribution-embedding scheme, which transforms the data from the observed state-variables with big noise to their distribution-variables with small noise, and thus makes the traditional criteria effective because of the significantly reduced fluctuations. Specifically, increasing the dimension of the observed data by moment expansion that changes the system from state-dynamics to probability distribution-dynamics, we derive new data in a higher-dimensional space but with much smaller noise. Then, we develop a criterion based on the dynamical network marker (DNM) to signal the impending critical transition using the transformed higher-dimensional data. We also demonstrate the effectiveness of our method in biological, ecological and financial systems.

  17. Weak and Dynamic GNSS Signal Tracking Strategies for Flight Missions in the Space Service Volume

    PubMed Central

    Jing, Shuai; Zhan, Xingqun; Liu, Baoyu; Chen, Maolin

    2016-01-01

    Weak-signal and high-dynamics are of two primary concerns of space navigation using GNSS (Global Navigation Satellite System) in the space service volume (SSV). The paper firstly defines a reference assumption third-order phase-locked loop (PLL) as the baseline of an onboard GNSS receiver, and proves the incompetence of this conventional architecture. Then an adaptive four-state Kalman filter (KF)-based algorithm is introduced to realize the optimization of loop noise bandwidth, which can adaptively regulate its filter gain according to the received signal power and line-of-sight (LOS) dynamics. To overcome the matter of losing lock in weak-signal and high-dynamic environments, an open loop tracking strategy aided by an inertial navigation system (INS) is recommended, and the traditional maximum likelihood estimation (MLE) method is modified in a non-coherent way by reconstructing the likelihood cost function. Furthermore, a typical mission with combined orbital maneuvering and non-maneuvering arcs is taken as a destination object to test the two proposed strategies. Finally, the experiment based on computer simulation identifies the effectiveness of an adaptive four-state KF-based strategy under non-maneuvering conditions and the virtue of INS-assisted methods under maneuvering conditions. PMID:27598164

  18. Label-Free Imaging of Dynamic and Transient Calcium Signaling in Single Cells.

    PubMed

    Lu, Jin; Li, Jinghong

    2015-11-09

    Cell signaling consists of diverse events that occur at various temporal and spatial scales, ranging from milliseconds to hours and from single biomolecules to cell populations. The pathway complexities require the development of new techniques that detect the overall signaling activities and are not limited to quantifying a single event. A plasmonic-based electrochemical impedance microscope (P-EIM) that can provide such data with excellent temporal and spatial resolution and does not require the addition of any labels for detection has now been developed. The highly dynamic and transient calcium signaling activities at the early stage of G-protein-coupled receptor (GPCR) stimulation were thus studied. It could be shown that a subpopulation of cells is more responsive towards agonist stimulation, and the heterogeneity of the local distributions and the transient activities of the ion channels during agonist-activated calcium flux in single HeLa cells were investigated.

  19. A Coupled Phase-Temperature Model for Dynamics of Transient Neuronal Signal in Mammals Cold Receptor

    PubMed Central

    Kirana, Firman Ahmad; Husein, Irzaman Sulaiman

    2016-01-01

    We propose a theoretical model consisting of coupled differential equation of membrane potential phase and temperature for describing the neuronal signal in mammals cold receptor. Based on the results from previous work by Roper et al., we modified a nonstochastic phase model for cold receptor neuronal signaling dynamics in mammals. We introduce a new set of temperature adjusted functional parameters which allow saturation characteristic at high and low steady temperatures. The modified model also accommodates the transient neuronal signaling process from high to low temperature by introducing a nonlinear differential equation for the “effective temperature” changes which is coupled to the phase differential equation. This simple model can be considered as a candidate for describing qualitatively the physical mechanism of the corresponding transient process. PMID:27774102

  20. Dynamic pathway modeling of signal transduction networks: a domain-oriented approach.

    PubMed

    Conzelmann, Holger; Gilles, Ernst-Dieter

    2008-01-01

    Mathematical models of biological processes become more and more important in biology. The aim is a holistic understanding of how processes such as cellular communication, cell division, regulation, homeostasis, or adaptation work, how they are regulated, and how they react to perturbations. The great complexity of most of these processes necessitates the generation of mathematical models in order to address these questions. In this chapter we provide an introduction to basic principles of dynamic modeling and highlight both problems and chances of dynamic modeling in biology. The main focus will be on modeling of s transduction pathways, which requires the application of a special modeling approach. A common pattern, especially in eukaryotic signaling systems, is the formation of multi protein signaling complexes. Even for a small number of interacting proteins the number of distinguishable molecular species can be extremely high. This combinatorial complexity is due to the great number of distinct binding domains of many receptors and scaffold proteins involved in signal transduction. However, these problems can be overcome using a new domain-oriented modeling approach, which makes it possible to handle complex and branched signaling pathways.

  1. Cellular context–mediated Akt dynamics regulates MAP kinase signaling thresholds during angiogenesis

    PubMed Central

    Hellesøy, Monica; Lorens, James B.

    2015-01-01

    The formation of new blood vessels by sprouting angiogenesis is tightly regulated by contextual cues that affect angiogeneic growth factor signaling. Both constitutive activation and loss of Akt kinase activity in endothelial cells impair angiogenesis, suggesting that Akt dynamics mediates contextual microenvironmental regulation. We explored the temporal regulation of Akt in endothelial cells during formation of capillary-like networks induced by cell–cell contact with vascular smooth muscle cells (vSMCs) and vSMC-associated VEGF. Expression of constitutively active Akt1 strongly inhibited network formation, whereas hemiphosphorylated Akt1 epi-alleles with reduced kinase activity had an intermediate inhibitory effect. Conversely, inhibition of Akt signaling did not affect endothelial cell migration or morphogenesis in vSMC cocultures that generate capillary-like structures. We found that endothelial Akt activity is transiently blocked by proteasomal degradation in the presence of SMCs during the initial phase of capillary-like structure formation. Suppressed Akt activity corresponded to the increased endothelial MAP kinase signaling that was required for angiogenic endothelial morphogenesis. These results reveal a regulatory principle by which cellular context regulates Akt protein dynamics, which determines MAP kinase signaling thresholds necessary drive a morphogenetic program during angiogenesis. PMID:26023089

  2. Epileptic seizures as condensed sleep: an analysis of network dynamics from electroencephalogram signals.

    PubMed

    Gast, Heidemarie; Müller, Markus; Rummel, Christian; Roth, Corinne; Mathis, Johannes; Schindler, Kaspar; Bassetti, Claudio L

    2014-06-01

    Both deepening sleep and evolving epileptic seizures are associated with increasing slow-wave activity. Larger-scale functional networks derived from electroencephalogram indicate that in both transitions dramatic changes of communication between brain areas occur. During seizures these changes seem to be 'condensed', because they evolve more rapidly than during deepening sleep. Here we set out to assess quantitatively functional network dynamics derived from electroencephalogram signals during seizures and normal sleep. Functional networks were derived from electroencephalogram signals from wakefulness, light and deep sleep of 12 volunteers, and from pre-seizure, seizure and post-seizure time periods of 10 patients suffering from focal onset pharmaco-resistant epilepsy. Nodes of the functional network represented electrical signals recorded by single electrodes and were linked if there was non-random cross-correlation between the two corresponding electroencephalogram signals. Network dynamics were then characterized by the evolution of global efficiency, which measures ease of information transmission. Global efficiency was compared with relative delta power. Global efficiency significantly decreased both between light and deep sleep, and between pre-seizure, seizure and post-seizure time periods. The decrease of global efficiency was due to a loss of functional links. While global efficiency decreased significantly, relative delta power increased except between the time periods wakefulness and light sleep, and pre-seizure and seizure. Our results demonstrate that both epileptic seizures and deepening sleep are characterized by dramatic fragmentation of larger-scale functional networks, and further support the similarities between sleep and seizures.

  3. Automated region of interest analysis of dynamic Ca2+ signals in image sequences

    PubMed Central

    Francis, Michael; Qian, Xun; Charbel, Chimène; Ledoux, Jonathan; Parker, J. C.

    2012-01-01

    Ca2+ signals are commonly measured using fluorescent Ca2+ indicators and microscopy techniques, but manual analysis of Ca2+ measurements is time consuming and subject to bias. Automated region of interest (ROI) detection algorithms have been employed for identification of Ca2+ signals in one-dimensional line scan images, but currently there is no process to integrate acquisition and analysis of ROIs within two-dimensional time lapse image sequences. Therefore we devised a novel algorithm for rapid ROI identification and measurement based on the analysis of best-fit ellipses assigned to signals within noise-filtered image sequences. This algorithm was implemented as a plugin for ImageJ software (National Institutes of Health, Bethesda, MD). We evaluated the ability of our algorithm to detect synthetic Gaussian signal pulses embedded in background noise. The algorithm placed ROIs very near to the center of a range of signal pulses, resulting in mean signal amplitude measurements of 99.06 ± 4.11% of true amplitude values. As a practical application, we evaluated both agonist-induced Ca2+ responses in cultured endothelial cell monolayers, and subtle basal endothelial Ca2+ dynamics in opened artery preparations. Our algorithm enabled comprehensive measurement of individual and localized cellular responses within cultured cell monolayers. It also accurately identified characteristic Ca2+ transients, or Ca2+ pulsars, within the endothelium of intact mouse mesenteric arteries and revealed the distribution of this basal Ca2+ signal modality to be non-Gaussian with respect to amplitude, duration, and spatial spread. We propose that large-scale statistical evaluations made possible by our algorithm will lead to a more efficient and complete characterization of physiologic Ca2+-dependent signaling. PMID:22538238

  4. Evaluating dynamic global vegetation models using meta-data analyses on soil carbon changes following land use change

    NASA Astrophysics Data System (ADS)

    Nyawira, Sylvia; Don, Axel; Nabel, Julia; Brovkin, Victor; Pongratz, Julia

    2015-04-01

    A major driver of changes in soil carbon in recent centuries has been land-use change. While evidence of land-use-related soil carbon changes exists based on local-scale observations, global estimates of these changes rely on modeling and remain highly uncertain. To understand the applicability of models to making future projections of soil carbon changes due to land use change, it is important to evaluate models using observations on soil carbon. A range of meta-data analyses on soil carbon changes following land use change has been published recently, aggregating local observations to levels potentially applicable to dynamic global vegetation models (DGVMs). However, up to now, this data has not been compared to DGVM simulations. The aim of this work is to develop an approach for evaluating DGVMs using these meta-analyses and apply the approach to evaluate the newly implemented soil carbon scheme-YASSO in the DGVM-JSBACH. YASSO is driven by vegetation productivity from JSBACH. However, the productivity by JSBACH is known to have biases in some regions as compared to what is observed in reality. To account for these biases, we confine the litter inputs to soils close to observations and constrain the decomposition by forcing YASSO with observed vegetation productivity and climate. Later we assess the bias introduced by JSBACH vegetation productivity on the soil carbon response in YASSO. We perform idealized simulations from one land-use to another to mimic the observational set-ups that the meta-data analyses comprise. To compare the simulated soil carbon response in the model with the meta-data, we select homogeneous physical regions based on the factors identified in literature as to influence the spatial and temporal variability of changes in soil carbon following land use change. Both the simulated equilibrium and the transient response of soil carbon to land use change simulated by YASSO for these regions is then compared with the meta-data analyses.

  5. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

    PubMed Central

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal

    2016-01-01

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. PMID:26728857

  6. Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling

    PubMed Central

    Wen, Ya; Alshikho, Mohamad J.; Herbert, Martha R.

    2016-01-01

    We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging—they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)—and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process “calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK” is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG’s category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic

  7. A digital-signal-processor-based optical tomographic system for dynamic imaging of joint diseases

    NASA Astrophysics Data System (ADS)

    Lasker, Joseph M.

    Over the last decade, optical tomography (OT) has emerged as viable biomedical imaging modality. Various imaging systems have been developed that are employed in preclinical as well as clinical studies, mostly targeting breast imaging, brain imaging, and cancer related studies. Of particular interest are so-called dynamic imaging studies where one attempts to image changes in optical properties and/or physiological parameters as they occur during a system perturbation. To successfully perform dynamic imaging studies, great effort is put towards system development that offers increasingly enhanced signal-to-noise performance at ever shorter data acquisition times, thus capturing high fidelity tomographic data within narrower time periods. Towards this goal, I have developed in this thesis a dynamic optical tomography system that is, unlike currently available analog instrumentation, based on digital data acquisition and filtering techniques. At the core of this instrument is a digital signal processor (DSP) that collects, collates, and processes the digitized data set. Complementary protocols between the DSP and a complex programmable logic device synchronizes the sampling process and organizes data flow. Instrument control is implemented through a comprehensive graphical user interface which integrates automated calibration, data acquisition, and signal post-processing. Real-time data is generated at frame rates as high as 140 Hz. An extensive dynamic range (˜190 dB) accommodates a wide scope of measurement geometries and tissue types. Performance analysis demonstrates very low system noise (˜1 pW rms noise equivalent power), excellent signal precision (˜0.04%--0.2%) and long term system stability (˜1% over 40 min). Experiments on tissue phantoms validate spatial and temporal accuracy of the system. As a potential new application of dynamic optical imaging I present the first application of this method to use vascular hemodynamics as a means of characterizing

  8. The relation of signal transduction to the sensitivity and dynamic range of bacterial chemotaxis.

    PubMed

    Namba, Toshinori; Nishikawa, Masatoshi; Shibata, Tatsuo

    2012-09-19

    Complex networks of interacting molecular components of living cells are responsible for many important processes, such as signal processing and transduction. An important challenge is to understand how the individual properties of these molecular interactions and biochemical transformations determine the system-level properties of biological functions. Here, we address the issue of the accuracy of signal transduction performed by a bacterial chemotaxis system. The chemotaxis sensitivity of bacteria to a chemoattractant gradient has been measured experimentally from bacterial aggregation in a chemoattractant-containing capillary. The observed precision of the chemotaxis depended on environmental conditions such as the concentration and molecular makeup of the chemoattractant. In a quantitative model, we derived the chemotactic response function, which is essential to describing the signal transduction process involved in bacterial chemotaxis. In the presence of a gradient, an analytical solution is derived that reveals connections between the chemotaxis sensitivity and the characteristics of the signaling system, such as reaction rates. These biochemical parameters are integrated into two system-level parameters: one characterizes the efficiency of gradient sensing, and the other is related to the dynamic range of chemotaxis. Thus, our approach explains how a particular signal transduction property affects the system-level performance of bacterial chemotaxis. We further show that the two parameters can be derived from published experimental data from a capillary assay, which successfully characterizes the performance of bacterial chemotaxis.

  9. Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation

    PubMed Central

    Collins, Anne L.; Greenfield, Venuz Y.; Bye, Jeffrey K.; Linker, Kay E.; Wang, Alice S.; Wassum, Kate M.

    2016-01-01

    Prolonged mesolimbic dopamine concentration changes have been detected during spatial navigation, but little is known about the conditions that engender this signaling profile or how it develops with learning. To address this, we monitored dopamine concentration changes in the nucleus accumbens core of rats throughout acquisition and performance of an instrumental action sequence task. Prolonged dopamine concentration changes were detected that ramped up as rats executed each action sequence and declined after earned reward collection. With learning, dopamine concentration began to rise increasingly earlier in the execution of the sequence and ultimately backpropagated away from stereotyped sequence actions, becoming only transiently elevated by the most distal and unexpected reward predictor. Action sequence-related dopamine signaling was reactivated in well-trained rats if they became disengaged in the task and in response to an unexpected change in the value, but not identity of the earned reward. Throughout training and test, dopamine signaling correlated with sequence performance. These results suggest that action sequences can engender a prolonged mode of dopamine signaling in the nucleus accumbens core and that such signaling relates to elements of the motivation underlying sequence execution and is dynamic with learning, overtraining and violations in reward expectation. PMID:26869075

  10. A parallel unbalanced digitization architecture to reduce the dynamic range of multiple signals

    NASA Astrophysics Data System (ADS)

    Vallérian, Mathieu; HuÅ£u, Florin; Villemaud, Guillaume; Miscopein, Benoît; Risset, Tanguy

    2016-05-01

    Technologies employed in urban sensor networks are permanently evolving, and thus the gateways employed to collect data in such kind of networks have to be very flexible in order to be compliant with the new communication standards. A convenient way to do that is to digitize all the received signals in one shot and then to digitally perform the signal processing, as it is done in software-defined radio (SDR). All signals can be emitted with very different features (bandwidth, modulation type, and power level) in order to respond to the various propagation conditions. Their difference in terms of power levels is a problem when digitizing them together, as no current commercial analog-to-digital converter (ADC) can provide a fine enough resolution to digitize this high dynamic range between the weakest possible signal in the presence of a stronger signal. This paper presents an RF front end receiver architecture capable of handling this problem by using two ADCs of lower resolutions. The architecture is validated through a set of simulations using Keysight's ADS software. The main validation criterion is the bit error rate comparison with a classical receiver.

  11. S-EMG signal compression based on domain transformation and spectral shape dynamic bit allocation

    PubMed Central

    2014-01-01

    Background Surface electromyographic (S-EMG) signal processing has been emerging in the past few years due to its non-invasive assessment of muscle function and structure and because of the fast growing rate of digital technology which brings about new solutions and applications. Factors such as sampling rate, quantization word length, number of channels and experiment duration can lead to a potentially large volume of data. Efficient transmission and/or storage of S-EMG signals are actually a research issue. That is the aim of this work. Methods This paper presents an algorithm for the data compression of surface electromyographic (S-EMG) signals recorded during isometric contractions protocol and during dynamic experimental protocols such as the cycling activity. The proposed algorithm is based on discrete wavelet transform to proceed spectral decomposition and de-correlation, on a dynamic bit allocation procedure to code the wavelets transformed coefficients, and on an entropy coding to minimize the remaining redundancy and to pack all data. The bit allocation scheme is based on mathematical decreasing spectral shape models, which indicates a shorter digital word length to code high frequency wavelets transformed coefficients. Four bit allocation spectral shape methods were implemented and compared: decreasing exponential spectral shape, decreasing linear spectral shape, decreasing square-root spectral shape and rotated hyperbolic tangent spectral shape. Results The proposed method is demonstrated and evaluated for an isometric protocol and for a dynamic protocol using a real S-EMG signal data bank. Objective performance evaluations metrics are presented. In addition, comparisons with other encoders proposed in scientific literature are shown. Conclusions The decreasing bit allocation shape applied to the quantized wavelet coefficients combined with arithmetic coding results is an efficient procedure. The performance comparisons of the proposed S-EMG data

  12. Flow dynamics of stenotic aortic valves assessed by signal processing of Doppler spectrograms.

    PubMed

    Bermejo, J; Antoranz, J C; García-Fernández, M A; Moreno, M M; Delcán, J L

    2000-03-01

    Clinical assessment of aortic stenosis (AS) is sometimes challenging, because all hemodynamic indexes of severity are modified by flow rate. However, the mechanisms underlying flow dependence remain controversial. Analysis of instantaneous flow dynamics has provided crucial information in a number of cardiovascular disorders and may add new insight into this phenomenon. This study was designed to analyze in vivo the effects of flow interventions on instantaneous valvular dynamics of stenotic valves. For this purpose, a custom algorithm for signal processing of Doppler spectrograms was developed and validated against a control population. Digital Doppler recordings at the aortic valve and left ventricular outflow tract were obtained in 15 patients with AS, at baseline and during low-dose dobutamine infusion; 10 normal subjects were studied as controls. Spectrograms were processed by signal averaging, time alignment, modal-velocity enhancement, envelope tracing, and numerical interpolation. Instantaneous relative aortic valve area (rAVA) was obtained by the continuity equation and plotted against normalized ejection time. Curves were classified as either type A (rapid, early-systolic opening) or type B (slow, end-systolic opening). Curves from controls closely matched prior knowledge of normal valve dynamics, but curves from patients were clearly different: all controls except 2 (80%) had type A, whereas all patients except 3 (80%) had a type B pattern (p = 0.03). Dobutamine infusion in patients increased and slightly anticipated peak rAVA by accelerating valve opening. Despite similar values of area and pressure difference, type B dynamics were associated with lower blood pressure (p = 0.01) and worse long-term outcome (>3 years) than type A flow dynamics (p = 0.02). Signal processing of Doppler spectrograms allows a comprehensive assessment of aortic flow dynamics. Differences in timing of valve aperture and in maximal leaflet excursion account for flow

  13. Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal

    PubMed Central

    Kiviniemi, Vesa; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Haapea, Marianne; Silven, Olli; Tervonen, Osmo

    2009-01-01

    Temporal blood oxygen level dependent (BOLD) contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD) trends of the form 1/fα. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF) after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H) characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow. PMID:19636388

  14. Static and dynamic analyses on the MFTF (Mirror Fusion Test Facility)-B Axicell Vacuum Vessel System: Final report

    SciTech Connect

    Ng, D.S.

    1986-09-01

    The Mirror Fusion Test Facility (MFTF-B) at Lawrence Livermore National Laboratory (LLNL) is a large-scale, tandem-mirror-fusion experiment. MFTF-B comprises many highly interconnected systems, including a magnet array and a vacuum vessel. The vessel, which houses the magnet array, is supported by reinforced concrete piers and steel frames resting on an array of foundations and surrounded by a 7-ft-thick concrete shielding vault. The Pittsburgh-Des Moines (PDM) Corporation, which was awarded the contract to design and construct the vessel, carried out fixed-base static and dynamic analyses of a finite-element model of the axicell vessel and magnet systems, including the simulation of various loading conditions and three postulated earthquake excitations. Meanwhile, LLNL monitored PDM's analyses with modeling studies of its own, and independently evaluated the structural responses of the vessel in order to define design criteria for the interface members and other project equipment. The assumptions underlying the finite-element model and the behavior of the axicell vessel are described in detail in this report, with particular emphasis placed on comparing the LLNL and PDM studies and on analyzing the fixed-base behavior with the soil-structure interaction, which occurs between the vessel and the massive concrete vault wall during a postulated seismic event. The structural members that proved sensitive to the soil effect are also reevaluated.

  15. Signal transduction controls heterogeneous NF-κB dynamics and target gene expression through cytokine-specific refractory states

    PubMed Central

    Adamson, Antony; Boddington, Christopher; Downton, Polly; Rowe, William; Bagnall, James; Lam, Connie; Maya-Mendoza, Apolinar; Schmidt, Lorraine; Harper, Claire V.; Spiller, David G.; Rand, David A.; Jackson, Dean A.; White, Michael R. H.; Paszek, Pawel

    2016-01-01

    Cells respond dynamically to pulsatile cytokine stimulation. Here we report that single, or well-spaced pulses of TNFα (>100 min apart) give a high probability of NF-κB activation. However, fewer cells respond to shorter pulse intervals (<100 min) suggesting a heterogeneous refractory state. This refractory state is established in the signal transduction network downstream of TNFR and upstream of IKK, and depends on the level of the NF-κB system negative feedback protein A20. If a second pulse within the refractory phase is IL-1β instead of TNFα, all of the cells respond. This suggests a mechanism by which two cytokines can synergistically activate an inflammatory response. Gene expression analyses show strong correlation between the cellular dynamic response and NF-κB-dependent target gene activation. These data suggest that refractory states in the NF-κB system constitute an inherent design motif of the inflammatory response and we suggest that this may avoid harmful homogenous cellular activation. PMID:27381163

  16. Super wavelet for sEMG signal extraction during dynamic fatiguing contractions.

    PubMed

    Al-Mulla, Mohamed R; Sepulveda, Francisco

    2015-01-01

    In this research an algorithm was developed to classify muscle fatigue content from dynamic contractions, by using a genetic algorithm (GA) and a pseudo-wavelet function. Fatiguing dynamic contractions of the biceps brachii were recorded using Surface Electromyography (sEMG) from thirteen subjects. Labelling the signal into two classes (Fatigue and Non-Fatigue) aided in the training and testing phase. The genetic algorithm was used to develop a pseudo-wavelet function that can optimally decompose the sEMG signal and classify the fatigue content of the signal. The evolved pseudo wavelet was tuned using the decomposition of 70% of the sEMG trials. 28 independent pseudo-wavelet evolution were run, after which the best run was selected and then tested on the remaining 30% of the trials to measure the classification performance. Results show that the evolved pseudo-wavelet improved the classification rate of muscle fatigue by 4.45 percentage points to 14.95 percentage points when compared to other standard wavelet functions (p<0.05), giving an average correct classification of 87.90%.

  17. Signaling and Dynamic Actin Responses of B Cells on Topographical Substrates

    NASA Astrophysics Data System (ADS)

    Ketchum, Christina; Sun, Xiaoyu; Fourkas, John; Song, Wenxia; Upadhyaya, Arpita

    B cells become activated upon physical contact with antigen on the surface of antigen presenting cells, such as dendritic cells. Binding of the B cell receptor with antigen initiates actin-mediated spreading of B cells, signaling cascades and eventually infection fighting antibodies. Lymphocytes, including B cells and T cells, have been shown to be responsive to the physical parameters of the contact surface, such as antigen mobility and substrate stiffness. However the roll of surface topography on lymphocyte function is unknown. Here we investigate the degree to which substrate topography controls actin-mediated spreading and B cell activation using nano-fabricated surfaces and live cell imaging. The model topographical system consists of 600 nanometer tall ridges with spacing varying between 800 nanometers and 5 micrometers. Using TIRF imaging we observe actin dynamics, B cell receptor motion and calcium signaling of B cells as they spread on the ridged substrates. We show that the spacing between ridges had a strong effect on the dynamics of actin and calcium influx on B cells. Our results indicate that B cells are highly sensitive to surface topography during cell spreading and signaling activation.

  18. Analog Filtering of Large Solvent Signals for Improved Dynamic Range in High-Resolution NMR

    NASA Astrophysics Data System (ADS)

    Redfield, A. G.; Kunz, S. D.

    1998-01-01

    The large solvent signal from samples in H2O solvent still challenges the dynamic range capability of any spectrometer. The solvent signal can be largely removed with a pair of simple resistor-capacitor (RC) high-pass filters when the solvent frequency is set at center band (zero frequency) using quadrature detection, withRC∼ 0.5 ms. However, an ∼0.5-ms transient remains at initial time, which we reduce fourfold for a short time only, just before the A/D converter, by means of a variable-gain amplifier, and later restore with software. This modification can result in a nearly fourfold increase in dynamic range. When we converted to a frequency-shifted mode (A. G. Redfield and S. D. Kunz, 1994,J. Magn. Reson. A108, 234-237) we replaced theRChigh-pass filter with a quadrature feedback notch filter tuned to the solvent frequency (5.06 kHz). This filter is an example of a class of two-input/two-output filters which maintain the spectral integrity (image-free character) of quadrature signals. Digital filters of the same type are also considered briefly. We discuss the implications of these ideas for spectrometer input design, including schemes for elimination of radiation damping, and effects of probe bandwidth on extreme oversampling.

  19. Analog filtering of large solvent signals for improved dynamic range in high-resolution NMR.

    PubMed

    Redfield, A G; Kunz, S D

    1998-01-01

    The large solvent signal from samples in H2O solvent still challenges the dynamic range capability of any spectrometer. The solvent signal can be largely removed with a pair of simple resistor-capacitor (RC) high-pass filters when the solvent frequency is set at center band (zero frequency) using quadrature detection, with RC approximately 0.5 ms. However, an approximately 0.5-ms transient remains at initial time, which we reduce fourfold for a short time only, just before the A/D converter, by means of a variable-gain amplifier, and later restore with software. This modification can result in a nearly fourfold increase in dynamic range. When we converted to a frequency-shifted mode (A. G. Redfield and S. D. Kunz, 1994, J. Magn. Reson. A 108, 234-237) we replaced the RC high-pass filter with a quadrature feedback notch filter tuned to the solvent frequency (5.06 kHz). This filter is an example of a class of two-input/two-output filters which maintain the spectral integrity (image-free character) of quadrature signals. Digital filters of the same type are also considered briefly. We discuss the implications of these ideas for spectrometer input design, including schemes for elimination of radiation damping, and effects of probe bandwidth on extreme oversampling.

  20. Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies

    PubMed Central

    Kolch, Walter; Kholodenko, Boris N.; Ambrosi, Cristina De; Barla, Annalisa; Biganzoli, Elia M.; Nencioni, Alessio; Patrone, Franco; Ballestrero, Alberto; Zoppoli, Gabriele; Verri, Alessandro; Parodi, Silvio

    2015-01-01

    The interconnected network of pathways downstream of the TGFβ, WNT and EGF-families of receptor ligands play an important role in colorectal cancer pathogenesis. We studied and implemented dynamic simulations of multiple downstream pathways and described the section of the signaling network considered as a Molecular Interaction Map (MIM). Our simulations used Ordinary Differential Equations (ODEs), which involved 447 reactants and their interactions. Starting from an initial “physiologic condition”, the model can be adapted to simulate individual pathologic cancer conditions implementing alterations/mutations in relevant onco-proteins. We verified some salient model predictions using the mutated colorectal cancer lines HCT116 and HT29. We measured the amount of MYC and CCND1 mRNAs and AKT and ERK phosphorylated proteins, in response to individual or combination onco-protein inhibitor treatments. Experimental and simulation results were well correlated. Recent independently published results were also predicted by our model. Even in the presence of an approximate and incomplete signaling network information, a predictive dynamic modeling seems already possible. An important long term road seems to be open and can be pursued further, by incremental steps, toward even larger and better parameterized MIMs. Personalized treatment strategies with rational associations of signaling-proteins inhibitors, could become a realistic goal. PMID:25671297

  1. The vav oncogene antagonises EGFR signalling and regulates adherens junction dynamics during Drosophila eye development.

    PubMed

    Martín-Bermudo, Maria-Dolores; Bardet, Pierre-Luc; Bellaïche, Yohanns; Malartre, Marianne

    2015-04-15

    Organ shaping and patterning depends on the coordinated regulation of multiple processes. The Drosophila compound eye provides an excellent model to study the coordination of cell fate and cell positioning during morphogenesis. Here, we find that loss of vav oncogene function during eye development is associated with a disorganised retina characterised by the presence of additional cells of all types. We demonstrate that these defects result from two distinct roles of Vav. First, and in contrast to its well-established role as a positive effector of the EGF receptor (EGFR), we show that readouts of the EGFR pathway are upregulated in vav mutant larval eye disc and pupal retina, indicating that Vav antagonises EGFR signalling during eye development. Accordingly, decreasing EGFR signalling in vav mutant eyes restores retinal organisation and rescues most vav mutant phenotypes. Second, using live imaging in the pupal retina, we observe that vav mutant cells do not form stable adherens junctions, causing various defects, such as recruitment of extra primary pigment cells. In agreement with this role in junction dynamics, we observe that these phenotypes can be exacerbated by lowering DE-Cadherin or Cindr levels. Taken together, our findings establish that Vav acts at multiple times during eye development to prevent excessive cell recruitment by limiting EGFR signalling and by regulating junction dynamics to ensure the correct patterning and morphogenesis of the Drosophila eye.

  2. Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies.

    PubMed

    Tortolina, Lorenzo; Duffy, David J; Maffei, Massimo; Castagnino, Nicoletta; Carmody, Aimée M; Kolch, Walter; Kholodenko, Boris N; De Ambrosi, Cristina; Barla, Annalisa; Biganzoli, Elia M; Nencioni, Alessio; Patrone, Franco; Ballestrero, Alberto; Zoppoli, Gabriele; Verri, Alessandro; Parodi, Silvio

    2015-03-10

    The interconnected network of pathways downstream of the TGFβ, WNT and EGF-families of receptor ligands play an important role in colorectal cancer pathogenesis.We studied and implemented dynamic simulations of multiple downstream pathways and described the section of the signaling network considered as a Molecular Interaction Map (MIM). Our simulations used Ordinary Differential Equations (ODEs), which involved 447 reactants and their interactions.Starting from an initial "physiologic condition", the model can be adapted to simulate individual pathologic cancer conditions implementing alterations/mutations in relevant onco-proteins. We verified some salient model predictions using the mutated colorectal cancer lines HCT116 and HT29. We measured the amount of MYC and CCND1 mRNAs and AKT and ERK phosphorylated proteins, in response to individual or combination onco-protein inhibitor treatments. Experimental and simulation results were well correlated. Recent independently published results were also predicted by our model.Even in the presence of an approximate and incomplete signaling network information, a predictive dynamic modeling seems already possible. An important long term road seems to be open and can be pursued further, by incremental steps, toward even larger and better parameterized MIMs. Personalized treatment strategies with rational associations of signaling-proteins inhibitors, could become a realistic goal.

  3. Emergence of complex dynamics in a simple model of signaling networks

    PubMed Central

    Amaral, Luís A. N.; Díaz-Guilera, Albert; Moreira, Andre A.; Goldberger, Ary L.; Lipsitz, Lewis A.

    2004-01-01

    Various physical, social, and biological systems generate complex fluctuations with correlations across multiple time scales. In physiologic systems, these long-range correlations are altered with disease and aging. Such correlated fluctuations in living systems have been attributed to the interaction of multiple control systems; however, the mechanisms underlying this behavior remain unknown. Here, we show that a number of distinct classes of dynamical behaviors, including correlated fluctuations characterized by 1/f scaling of their power spectra, can emerge in networks of simple signaling units. We found that, under general conditions, complex dynamics can be generated by systems fulfilling the following two requirements, (i) a “small-world” topology and (ii) the presence of noise. Our findings support two notable conclusions. First, complex physiologic-like signals can be modeled with a minimal set of components; and second, systems fulfilling conditions i and ii are robust to some degree of degradation (i.e., they will still be able to generate 1/f dynamics). PMID:15505227

  4. Advances in global sensitivity analyses of demographic-based species distribution models to address uncertainties in dynamic landscapes

    PubMed Central

    Curtis, Janelle M.R.

    2016-01-01

    Developing a rigorous understanding of multiple global threats to species persistence requires the use of integrated modeling methods that capture processes which influence species distributions. Species distribution models (SDMs) coupled with population dynamics models can incorporate relationships between changing environments and demographics and are increasingly used to quantify relative extinction risks associated with climate and land-use changes. Despite their appeal, uncertainties associated with complex models can undermine their usefulness for advancing predictive ecology and informing conservation management decisions. We developed a computationally-efficient and freely available tool (GRIP 2.0) that implements and automates a global sensitivity analysis of coupled SDM-population dynamics models for comparing the relative influence of demographic parameters and habitat attributes on predicted extinction risk. Advances over previous global sensitivity analyses include the ability to vary habitat suitability across gradients, as well as habitat amount and configuration of spatially-explicit suitability maps of real and simulated landscapes. Using GRIP 2.0, we carried out a multi-model global sensitivity analysis of a coupled SDM-population dynamics model of whitebark pine (Pinus albicaulis) in Mount Rainier National Park as a case study and quantified the relative influence of input parameters and their interactions on model predictions. Our results differed from the one-at-time analyses used in the original study, and we found that the most influential parameters included the total amount of suitable habitat within the landscape, survival rates, and effects of a prevalent disease, white pine blister rust. Strong interactions between habitat amount and survival rates of older trees suggests the importance of habitat in mediating the negative influences of white pine blister rust. Our results underscore the importance of considering habitat attributes along

  5. Advances in global sensitivity analyses of demographic-based species distribution models to address uncertainties in dynamic landscapes.

    PubMed

    Naujokaitis-Lewis, Ilona; Curtis, Janelle M R

    2016-01-01

    Developing a rigorous understanding of multiple global threats to species persistence requires the use of integrated modeling methods that capture processes which influence species distributions. Species distribution models (SDMs) coupled with population dynamics models can incorporate relationships between changing environments and demographics and are increasingly used to quantify relative extinction risks associated with climate and land-use changes. Despite their appeal, uncertainties associated with complex models can undermine their usefulness for advancing predictive ecology and informing conservation management decisions. We developed a computationally-efficient and freely available tool (GRIP 2.0) that implements and automates a global sensitivity analysis of coupled SDM-population dynamics models for comparing the relative influence of demographic parameters and habitat attributes on predicted extinction risk. Advances over previous global sensitivity analyses include the ability to vary habitat suitability across gradients, as well as habitat amount and configuration of spatially-explicit suitability maps of real and simulated landscapes. Using GRIP 2.0, we carried out a multi-model global sensitivity analysis of a coupled SDM-population dynamics model of whitebark pine (Pinus albicaulis) in Mount Rainier National Park as a case study and quantified the relative influence of input parameters and their interactions on model predictions. Our results differed from the one-at-time analyses used in the original study, and we found that the most influential parameters included the total amount of suitable habitat within the landscape, survival rates, and effects of a prevalent disease, white pine blister rust. Strong interactions between habitat amount and survival rates of older trees suggests the importance of habitat in mediating the negative influences of white pine blister rust. Our results underscore the importance of considering habitat attributes along

  6. Enhanced resting-state dynamics of the hemoglobin signal as a novel biomarker for detection of breast cancer

    PubMed Central

    Graber, Harry L.; Al abdi, Rabah; Xu, Yong; Asarian, Armand P.; Pappas, Peter J.; Dresner, Lisa; Patel, Naresh; Jagarlamundi, Kuppuswamy; Solomon, William B.; Barbour, Randall L.

    2015-01-01

    Purpose: The work presented here demonstrates an application of diffuse optical tomography (DOT) to the problem of breast-cancer diagnosis. The potential for using spatial and temporal variability measures of the hemoglobin signal to identify useful biomarkers was studied. Methods: DOT imaging data were collected using two instrumentation platforms the authors developed, which were suitable for exploring tissue dynamics while performing a simultaneous bilateral exam. For each component of the hemoglobin signal (e.g., total, oxygenated), the image time series was reduced to eight scalar metrics that were affected by one or more dynamic properties of the breast microvasculature (e.g., average amplitude, amplitude heterogeneity, strength of spatial coordination). Receiver-operator characteristic (ROC) analyses, comparing groups of subjects with breast cancer to various control groups (i.e., all noncancer subjects, only those with diagnosed benign breast pathology, and only those with no known breast pathology), were performed to evaluate the effect of cancer on the magnitudes of the metrics and of their interbreast differences and ratios. Results: For women with known breast cancer, simultaneous bilateral DOT breast measures reveal a marked increase in the resting-state amplitude of the vasomotor response in the hemoglobin signal for the affected breast, compared to the contralateral, noncancer breast. Reconstructed 3D spatial maps of observed dynamics also show that this behavior extends well beyond the tumor border. In an effort to identify biomarkers that have the potential to support clinical aims, a group of scalar quantities extracted from the time series measures was systematically examined. This analysis showed that many of the quantities obtained by computing paired responses from the bilateral scans (e.g., interbreast differences, ratios) reveal statistically significant differences between the cancer-positive and -negative subject groups, while the

  7. Enhanced resting-state dynamics of the hemoglobin signal as a novel biomarker for detection of breast cancer

    SciTech Connect

    Graber, Harry L. Xu, Yong; Barbour, Randall L.; Al abdi, Rabah; Asarian, Armand P.; Pappas, Peter J.; Dresner, Lisa; Patel, Naresh; Jagarlamundi, Kuppuswamy; Solomon, William B.

    2015-11-15

    Purpose: The work presented here demonstrates an application of diffuse optical tomography (DOT) to the problem of breast-cancer diagnosis. The potential for using spatial and temporal variability measures of the hemoglobin signal to identify useful biomarkers was studied. Methods: DOT imaging data were collected using two instrumentation platforms the authors developed, which were suitable for exploring tissue dynamics while performing a simultaneous bilateral exam. For each component of the hemoglobin signal (e.g., total, oxygenated), the image time series was reduced to eight scalar metrics that were affected by one or more dynamic properties of the breast microvasculature (e.g., average amplitude, amplitude heterogeneity, strength of spatial coordination). Receiver-operator characteristic (ROC) analyses, comparing groups of subjects with breast cancer to various control groups (i.e., all noncancer subjects, only those with diagnosed benign breast pathology, and only those with no known breast pathology), were performed to evaluate the effect of cancer on the magnitudes of the metrics and of their interbreast differences and ratios. Results: For women with known breast cancer, simultaneous bilateral DOT breast measures reveal a marked increase in the resting-state amplitude of the vasomotor response in the hemoglobin signal for the affected breast, compared to the contralateral, noncancer breast. Reconstructed 3D spatial maps of observed dynamics also show that this behavior extends well beyond the tumor border. In an effort to identify biomarkers that have the potential to support clinical aims, a group of scalar quantities extracted from the time series measures was systematically examined. This analysis showed that many of the quantities obtained by computing paired responses from the bilateral scans (e.g., interbreast differences, ratios) reveal statistically significant differences between the cancer-positive and -negative subject groups, while the

  8. Variability of a dynamic visual signal: the fiddler crab claw-waving display.

    PubMed

    How, Martin J; Zeil, Jochen; Hemmi, Jan M

    2009-01-01

    Fiddler crabs use elaborate, species-specific claw-waving displays to communicate with rivals and mates. However, detailed comparative studies of fiddler crab signal structure and structural variations are lacking. This paper provides an analysis of the claw-waving displays of seven Australian species of fiddler crab, Uca mjoebergi, U. perplexa, U. polita, U. seismella, U. signata, U. elegans and U. vomeris. We used digital video to record and analyse the fine-scale spatiotemporal properties of these movement-based visual signals. We found that the structure and timing of the displays is species-specific, exhibiting inter-specific differences that follow phylogenetic relationships. The displays showed intra-specific variation according to individual identity, geographic location and fine-scale behavioural context. The observed differences and variations are discussed in the light of the evolutionary forces that may shape their design.

  9. Combined Analyses of the VHL and Hypoxia Signaling Axes in an Isogenic Pairing of Renal Clear Cell Carcinoma Cells.

    PubMed

    Malec, Viktor; Coulson, Judy M; Urbé, Sylvie; Clague, Michael J

    2015-12-04

    The loss of function of the Von Hippel-Lindau (VHL) tumor suppressor leads to the development of hypervascular tumors, exemplified by clear-cell-type renal cell carcinoma (RCC). VHL governs the adaptive responses to fluctuation of oxygen levels largely through the regulated suppression of hypoxia inducible factors (HIFs). Here, we combine proteome and phospho-proteomic analysis of isogenic 786-O RCC (±VHL) cells to compare signatures that reflect hypoxia and/or loss of VHL. VHL-independent hypoxic responses, notably include up-regulation of phosphorylation at Ser232 on the pyruvate dehydrogenase α subunit that is known to promote glycolysis. Hypoxic responses governed by VHL include up-regulation of known biomarkers of RCC (e.g., GLUT1, NDRG1) and the signaling adaptor molecule IRS-2. Notably, we also observe down-regulation of linked-components associated with the Jacobs-Stewart cycle, including the intracellular carbonic anhydrase II (CA2), which governs cellular response to CO2 fluctuations that often accompany hypoxia in tumors. Further studies indicate an unusual mechanism of control for CA2 expression that, at least in part, reflects enhanced activity of the NFκB pathway, which is associated with loss of VHL.

  10. Identification of novel plant peroxisomal targeting signals by a combination of machine learning methods and in vivo subcellular targeting analyses.

    PubMed

    Lingner, Thomas; Kataya, Amr R; Antonicelli, Gerardo E; Benichou, Aline; Nilssen, Kjersti; Chen, Xiong-Yan; Siemsen, Tanja; Morgenstern, Burkhard; Meinicke, Peter; Reumann, Sigrun

    2011-04-01

    In the postgenomic era, accurate prediction tools are essential for identification of the proteomes of cell organelles. Prediction methods have been developed for peroxisome-targeted proteins in animals and fungi but are missing specifically for plants. For development of a predictor for plant proteins carrying peroxisome targeting signals type 1 (PTS1), we assembled more than 2500 homologous plant sequences, mainly from EST databases. We applied a discriminative machine learning approach to derive two different prediction methods, both of which showed high prediction accuracy and recognized specific targeting-enhancing patterns in the regions upstream of the PTS1 tripeptides. Upon application of these methods to the Arabidopsis thaliana genome, 392 gene models were predicted to be peroxisome targeted. These predictions were extensively tested in vivo, resulting in a high experimental verification rate of Arabidopsis proteins previously not known to be peroxisomal. The prediction methods were able to correctly infer novel PTS1 tripeptides, which even included novel residues. Twenty-three newly predicted PTS1 tripeptides were experimentally confirmed, and a high variability of the plant PTS1 motif was discovered. These prediction methods will be instrumental in identifying low-abundance and stress-inducible peroxisomal proteins and defining the entire peroxisomal proteome of Arabidopsis and agronomically important crop plants.

  11. Dynamic Faraday cup signal analysis and the measurement of energetic ions emitted by plasma focus

    SciTech Connect

    Pestehe, S. J. Mohammadnejad, M.; Irani Mobaraki, S.

    2014-03-15

    A theoretical model is developed to study the signals from a typical dynamic Faraday cup, and using this model the output signals from this structure are obtained. A detailed discussion on the signal structure, using different experimental conditions, is also given. It is argued that there is a possibility of determining the total charge of the generated ion pulse, the maximum velocity of the ions, ion velocity distribution, and the number of ion species for mixed working gases, under certain conditions. In addition, the number of different ionization stages, the number of different pinches in one shot, and the number of different existing acceleration mechanisms can also be determined provided that the mentioned conditions being satisfied. An experiment is carried out on the Filippov type 90 kJ Sahand plasma focus using Ar as the working gas at the pressure of 0.25 Torr. The data from a typical shot are fitted to a signal from the model and the total charge of the related energetic ion pulse is deduced using the values of the obtained fit parameters. Good agreement between the obtained amount of the total charge and the values obtained during other experiments on the same plasma focus device is observed.

  12. Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses

    PubMed Central

    Petrenko, Natalia; Chereji, Raˇzvan V.; McClean, Megan N.; Morozov, Alexandre V.; Broach, James R.

    2013-01-01

    All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to “hedge their bets” in responding to an uncertain future, and to balance growth and survival in an unpredictable environment. PMID:23615444

  13. Dynamic Faraday cup signal analysis and the measurement of energetic ions emitted by plasma focus

    NASA Astrophysics Data System (ADS)

    Pestehe, S. J.; Mohammadnejad, M.; Irani Mobaraki, S.

    2014-03-01

    A theoretical model is developed to study the signals from a typical dynamic Faraday cup, and using this model the output signals from this structure are obtained. A detailed discussion on the signal structure, using different experimental conditions, is also given. It is argued that there is a possibility of determining the total charge of the generated ion pulse, the maximum velocity of the ions, ion velocity distribution, and the number of ion species for mixed working gases, under certain conditions. In addition, the number of different ionization stages, the number of different pinches in one shot, and the number of different existing acceleration mechanisms can also be determined provided that the mentioned conditions being satisfied. An experiment is carried out on the Filippov type 90 kJ Sahand plasma focus using Ar as the working gas at the pressure of 0.25 Torr. The data from a typical shot are fitted to a signal from the model and the total charge of the related energetic ion pulse is deduced using the values of the obtained fit parameters. Good agreement between the obtained amount of the total charge and the values obtained during other experiments on the same plasma focus device is observed.

  14. ACTIN DEPOLYMERIZING FACTOR4 regulates actin dynamics during innate immune signaling in Arabidopsis.

    PubMed

    Henty-Ridilla, Jessica L; Li, Jiejie; Day, Brad; Staiger, Christopher J

    2014-01-01

    Conserved microbe-associated molecular patterns (MAMPs) are sensed by pattern recognition receptors (PRRs) on cells of plants and animals. MAMP perception typically triggers rearrangements to actin cytoskeletal arrays during innate immune signaling. However, the signaling cascades linking PRR activation by MAMPs to cytoskeleton remodeling are not well characterized. Here, we developed a system to dissect, at high spatial and temporal resolution, the regulation of actin dynamics during innate immune signaling in plant cells. Within minutes of MAMP perception, we detected changes to single actin filament turnover in epidermal cells treated with bacterial and fungal MAMPs. These MAMP-induced alterations phenocopied an ACTIN DEPOLYMERIZING FACTOR4 (ADF4) knockout mutant. Moreover, actin arrays in the adf4 mutant were unresponsive to a bacterial MAMP, elf26, but responded normally to the fungal MAMP, chitin. Together, our data provide strong genetic and cytological evidence for the inhibition of ADF activity regulating actin remodeling during innate immune signaling. This work is the first to directly link an ADF/cofilin to the cytoskeletal rearrangements elicited directly after pathogen perception in plant or mammalian cells.

  15. The dynamics of signal amplification by macromolecular assemblies for the control of chromosome segregation

    PubMed Central

    Lee, Semin; Bolanos-Garcia, Victor M.

    2014-01-01

    The control of chromosome segregation relies on the spindle assembly checkpoint (SAC), a complex regulatory system that ensures the high fidelity of chromosome segregation in higher organisms by delaying the onset of anaphase until each chromosome is properly bi-oriented on the mitotic spindle. Central to this process is the establishment of multiple yet specific protein-protein interactions in a narrow time-space window. Here we discuss the highly dynamic nature of multi-protein complexes that control chromosome segregation in which an intricate network of weak but cooperative interactions modulate signal amplification to ensure a proper SAC response. We also discuss the current structural understanding of the communication between the SAC and the kinetochore; how transient interactions can regulate the assembly and disassembly of the SAC as well as the challenges and opportunities for the definition and the manipulation of the flow of information in SAC signaling. PMID:25324779

  16. Aurora A drives early signalling and vesicle dynamics during T-cell activation.

    PubMed

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B; Sánchez-Madrid, Francisco

    2016-04-19

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal.

  17. Resolving dynamics of cell signaling via real-time imaging of the immunological synapse.

    SciTech Connect

    Stevens, Mark A.; Pfeiffer, Janet R.; Wilson, Bridget S.; Timlin, Jerilyn Ann; Thomas, James L.; Lidke, Keith A.; Spendier, Kathrin; Oliver, Janet M.; Carroll-Portillo, Amanda; Aaron, Jesse S.; Mirijanian, Dina T.; Carson, Bryan D.; Burns, Alan Richard; Rebeil, Roberto

    2009-10-01

    This highly interdisciplinary team has developed dual-color, total internal reflection microscopy (TIRF-M) methods that enable us to optically detect and track in real time protein migration and clustering at membrane interfaces. By coupling TIRF-M with advanced analysis techniques (image correlation spectroscopy, single particle tracking) we have captured subtle changes in membrane organization that characterize immune responses. We have used this approach to elucidate the initial stages of cell activation in the IgE signaling network of mast cells and the Toll-like receptor (TLR-4) response in macrophages stimulated by bacteria. To help interpret these measurements, we have undertaken a computational modeling effort to connect the protein motion and lipid interactions. This work provides a deeper understanding of the initial stages of cellular response to external agents, including dynamics of interaction of key components in the signaling network at the 'immunological synapse,' the contact region of the cell and its adversary.

  18. Aurora A drives early signalling and vesicle dynamics during T-cell activation

    PubMed Central

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B.; Sánchez-Madrid, Francisco

    2016-01-01

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal. PMID:27091106

  19. Dynamic BMP signaling polarized by Toll patterns the dorsoventral axis in a hemimetabolous insect

    PubMed Central

    Sachs, Lena; Chen, Yen-Ta; Drechsler, Axel; Lynch, Jeremy A; Panfilio, Kristen A; Lässig, Michael; Berg, Johannes; Roth, Siegfried

    2015-01-01

    Toll-dependent patterning of the dorsoventral axis in Drosophila represents one of the best understood gene regulatory networks. However, its evolutionary origin has remained elusive. Outside the insects Toll is not known for a patterning function, but rather for a role in pathogen defense. Here, we show that in the milkweed bug Oncopeltus fasciatus, whose lineage split from Drosophila's more than 350 million years ago, Toll is only required to polarize a dynamic BMP signaling network. A theoretical model reveals that this network has self-regulatory properties and that shallow Toll signaling gradients are sufficient to initiate axis formation. Such gradients can account for the experimentally observed twinning of insect embryos upon egg fragmentation and might have evolved from a state of uniform Toll activity associated with protecting insect eggs against pathogens. DOI: http://dx.doi.org/10.7554/eLife.05502.001 PMID:25962855

  20. Dynamics of the Bingham Canyon Mine landslides from seismic signal analysis

    NASA Astrophysics Data System (ADS)

    Hibert, Clément; Ekström, Göran; Stark, Colin P.

    2014-07-01

    Joint interpretation of long- and short-period seismic signals generated by landslides sheds light on the dynamics of slope failure, providing constraints on landslide initiation and termination and on the main phases of acceleration and deceleration. We carry out a combined analysis of the seismic signals generated by two massive landslides that struck the Bingham Canyon Mine pit on 10 April 2013. Inversion of the long-period waveforms yields time series for the bulk landslide forces and momenta, from which we deduce runout trajectories consistent with the deposit morphology. Comparing these time series with the short-period seismic data, we are able to infer when and where major changes take place in landslide momentum along the runout path. This combined analysis points to a progressive fracturing of the masses during acceleration indicates that deceleration starts the moment they reach the pit floor and suggests that the bulk movement is stopped by a topographic barrier.

  1. Quantitative Proteomic Analyses Identify ABA-Related Proteins and Signal Pathways in Maize Leaves under Drought Conditions.

    PubMed

    Zhao, Yulong; Wang, Yankai; Yang, Hao; Wang, Wei; Wu, Jianyu; Hu, Xiuli

    2016-01-01

    Drought stress is one of major factors resulting in maize yield loss. The roles of abscisic acid (ABA) have been widely studied in crops in response to drought stress. However, more attention is needed to identify key ABA-related proteins and also gain deeper molecular insights about drought stress in maize. Based on this need, the physiology and proteomics of the ABA-deficient maize mutant vp5 and its wild-type Vp5 under drought stress were examined and analyzed. Malondialdehyde content increased and quantum efficiency of photosystem II decreased under drought stress in both genotypes. However, the magnitude of the increase or decrease was significantly higher in vp5 than in Vp5. A total of 7051 proteins with overlapping expression patterns among three replicates in the two genotypes were identified by Multiplex run iTRAQ-based quantitative proteomic and liquid chromatography-tandem mass spectrometry methods, of which the expression of only 150 proteins (130 in Vp5, 27 in vp5) showed changes of at least 1.5-fold under drought stress. Among the 150 proteins, 67 and 60 proteins were up-regulated and down-regulated by drought stress in an ABA-dependent way, respectively. ABA was found to play active roles in regulating signaling pathways related to photosynthesis, oxidative phosphorylation (mainly related to ATP synthesis), and glutathione metabolism (involved in antioxidative reaction) in the maize response to drought stress. Our results provide an extensive dataset of ABA-dependent, drought-regulated proteins in maize plants, which may help to elucidate the underlying mechanisms of ABA-enhanced tolerance to drought stress in maize.

  2. Quantitative Proteomic Analyses Identify ABA-Related Proteins and Signal Pathways in Maize Leaves under Drought Conditions

    PubMed Central

    Zhao, Yulong; Wang, Yankai; Yang, Hao; Wang, Wei; Wu, Jianyu; Hu, Xiuli

    2016-01-01

    Drought stress is one of major factors resulting in maize yield loss. The roles of abscisic acid (ABA) have been widely studied in crops in response to drought stress. However, more attention is needed to identify key ABA-related proteins and also gain deeper molecular insights about drought stress in maize. Based on this need, the physiology and proteomics of the ABA-deficient maize mutant vp5 and its wild-type Vp5 under drought stress were examined and analyzed. Malondialdehyde content increased and quantum efficiency of photosystem II decreased under drought stress in both genotypes. However, the magnitude of the increase or decrease was significantly higher in vp5 than in Vp5. A total of 7051 proteins with overlapping expression patterns among three replicates in the two genotypes were identified by Multiplex run iTRAQ-based quantitative proteomic and liquid chromatography-tandem mass spectrometry methods, of which the expression of only 150 proteins (130 in Vp5, 27 in vp5) showed changes of at least 1.5-fold under drought stress. Among the 150 proteins, 67 and 60 proteins were up-regulated and down-regulated by drought stress in an ABA-dependent way, respectively. ABA was found to play active roles in regulating signaling pathways related to photosynthesis, oxidative phosphorylation (mainly related to ATP synthesis), and glutathione metabolism (involved in antioxidative reaction) in the maize response to drought stress. Our results provide an extensive dataset of ABA-dependent, drought-regulated proteins in maize plants, which may help to elucidate the underlying mechanisms of ABA-enhanced tolerance to drought stress in maize. PMID:28008332

  3. Multiple Model-Informed Open-Loop Control of Uncertain Intracellular Signaling Dynamics

    PubMed Central

    Perley, Jeffrey P.; Mikolajczak, Judith; Harrison, Marietta L.; Buzzard, Gregery T.; Rundell, Ann E.

    2014-01-01

    Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs). These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  4. Signalling crosstalk at the leading edge controls tissue closure dynamics in the Drosophila embryo

    PubMed Central

    Carballès, Fabrice; Parassol, Nadège; Schaub, Sébastien; Cérézo, Delphine; Noselli, Stéphane

    2017-01-01

    Tissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGFβ/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we sought out new JNK target genes through a genomic approach: 25 were identified of which 8 are specifically expressed in the LE, similarly to decapentaplegic or puckered. Quantitative in situ gene profiling of this new set of LE genes reveals complex patterning of the LE along the AP axis, involving a three-way interplay between the JNK pathway, segmentation and HOX genes. Patterning of the LE into discrete domains appears essential for coordination of tissue sealing dynamics. Loss of anterior or posterior HOX gene function leads to strongly delayed and asymmetric DC, due to incorrect zipping in their respective functional domain. Therefore, in addition to significantly increasing the number of JNK target genes identified so far, our results reveal that the LE is a highly heterogeneous morphogenetic organizer, sculpted through crosstalk between JNK, segmental and AP signalling. This fine-tuning regulatory mechanism is essential to coordinate morphogenesis and dynamics of tissue sealing. PMID:28231245

  5. Mitochondria are the source of hydrogen peroxide for dynamic brain-cell signaling

    PubMed Central

    Bao, Li; Avshalumov, Marat V.; Patel, Jyoti C.; Lee, Christian R.; Miller, Evan W.; Chang, Christopher J.; Rice, Margaret E.

    2010-01-01

    Hydrogen peroxide (H2O2) is emerging as a ubiquitous small-molecule messenger in biology, particularly in the brain, but underlying mechanisms of peroxide signaling remain an open frontier for study. For example, dynamic dopamine transmission in dorsolateral striatum is regulated on a subsecond timescale by glutamate via H2O2 signaling, which activates ATP-sensitive potassium (KATP) channels to inhibit dopamine release. However, the origin of this modulatory H2O2 has been elusive. Here we addressed three possible sources of H2O2 produced for rapid neuronal signaling in striatum: mitochondrial respiration; monoamine oxidase (MAO); and NADPH oxidase (Nox). Evoked dopamine release in guinea-pig striatal slices was monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Using direct fluorescence imaging of H2O2 and tissue analysis of ATP, we found that co-application of rotenone (50 nM), a mitochondrial complex I inhibitor, and succinate (5 mM), a complex II substrate, limited H2O2 production, but maintained tissue ATP content. Strikingly, co-application of rotenone and succinate also prevented glutamate-dependent regulation of dopamine release, implicating mitochondrial H2O2 in release modulation. By contrast, inhibitors of MAO or Nox had no effect on dopamine release, suggesting a limited role for these metabolic enzymes in rapid H2O2 production in the striatum. These data provide the first demonstration that respiring mitochondria are the primary source of H2O2 generation for dynamic neuronal signaling. PMID:19605638

  6. Mitochondria are the source of hydrogen peroxide for dynamic brain-cell signaling.

    PubMed

    Bao, Li; Avshalumov, Marat V; Patel, Jyoti C; Lee, Christian R; Miller, Evan W; Chang, Christopher J; Rice, Margaret E

    2009-07-15

    Hydrogen peroxide (H(2)O(2)) is emerging as a ubiquitous small-molecule messenger in biology, particularly in the brain, but underlying mechanisms of peroxide signaling remain an open frontier for study. For example, dynamic dopamine transmission in dorsolateral striatum is regulated on a subsecond timescale by glutamate via H(2)O(2) signaling, which activates ATP-sensitive potassium (K(ATP)) channels to inhibit dopamine release. However, the origin of this modulatory H(2)O(2) has been elusive. Here we addressed three possible sources of H(2)O(2) produced for rapid neuronal signaling in striatum: mitochondrial respiration, monoamine oxidase (MAO), and NADPH oxidase (Nox). Evoked dopamine release in guinea-pig striatal slices was monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Using direct fluorescence imaging of H(2)O(2) and tissue analysis of ATP, we found that coapplication of rotenone (50 nM), a mitochondrial complex I inhibitor, and succinate (5 mM), a complex II substrate, limited H(2)O(2) production, but maintained tissue ATP content. Strikingly, coapplication of rotenone and succinate also prevented glutamate-dependent regulation of dopamine release, implicating mitochondrial H(2)O(2) in release modulation. In contrast, inhibitors of MAO or Nox had no effect on dopamine release, suggesting a limited role for these metabolic enzymes in rapid H(2)O(2) production in the striatum. These data provide the first demonstration that respiring mitochondria are the primary source of H(2)O(2) generation for dynamic neuronal signaling.

  7. Multiple model-informed open-loop control of uncertain intracellular signaling dynamics.

    PubMed

    Perley, Jeffrey P; Mikolajczak, Judith; Harrison, Marietta L; Buzzard, Gregery T; Rundell, Ann E

    2014-04-01

    Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs). These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  8. Molecular Dynamics Investigation of a Mechanism of Allosteric Signal Transmission in Ribosomes.

    PubMed

    Makarov, G I; Golovin, A V; Sumbatyan, N V; Bogdanov, A A

    2015-08-01

    The ribosome is a molecular machine that synthesizes all cellular proteins via translation of genetic information encoded in polynucleotide chain of messenger RNA. Transition between different stages of the ribosome working cycle is strictly coordinated by changes in structure and mutual position both of subunits of the ribosome and its ligands. Therein, information regarding structural transformations is transmitted between functional centers of the ribosome through specific signals. Usually, functional centers of ribosomes are located at a distance reaching up to several tens of angstroms, and it is believed that such signals are transduced allosterically. In our study, we attempted to answer the question of how allosteric signal can be transmitted from one of the so-called sensory elements of ribosomal tunnel (RT) to the peptidyl transferase center (PTC). A segment of RT wall from the E. coli ribosome composed of nucleotide residues A2058, A2059, m(2)A2503, G2061, A2062, and C2063 of its 23S rRNA was examined by molecular dynamics simulations. It was found that a potential signal transduction pathway A2058-C2063 acted as a dynamic ensemble of interdependent conformational states, wherein cascade-like changes can occur. It was assumed that structural rearrangement in the A2058-C2063 RT segment results in reversible inactivation of PTC due to a strong stacking contact between functionally important U2585 residue of the PTC and nucleotide residue C2063. A potential role for the observed conformational transition in the A2058-C2063 segment for regulating ribosome activity is discussed.

  9. Integrative Analyses of Uterine Transcriptome and MicroRNAome Reveal Compromised LIF-STAT3 Signaling and Progesterone Response in the Endometrium of Patients with Recurrent/Repeated Implantation Failure (RIF).

    PubMed

    Choi, Youngsok; Kim, Hye-Ryun; Lim, Eun Jin; Park, Miseon; Yoon, Jung Ah; Kim, Yeon Sun; Kim, Eun-Kyung; Shin, Ji-Eun; Kim, Ji Hyang; Kwon, Hwang; Song, Haengseok; Choi, Dong-Hee

    2016-01-01

    Intimate two-way interactions between the implantation-competent blastocyst and receptive uterus are prerequisite for successful embryo implantation. In humans, recurrent/repeated implantation failure (RIF) may occur due to altered uterine receptivity with aberrant gene expression in the endometrium as well as genetic defects in embryos. Several studies have been performed to understand dynamic changes of uterine transcriptome during menstrual cycles in humans. However, uterine transcriptome of the patients with RIF has not been clearly investigated yet. Here we show that several signaling pathways as well as many genes and microRNAs are dysregulated in the endometrium of patients with RIF (RIFE). Whereas unsupervised hierarchical clustering showed that overall mRNA and microRNA profiles of RIFE were similar to those of endometria of healthy women, many genes were significantly dysregulated in RIFE (cut off at 1.5 fold change). The majority (~75%) of differentially expressed genes in RIFE including S100 calcium binding protein P (S100P), Chemokine (C-X-C motif) ligand 13 (CXCL13) and SIX homeobox 1 (SIX1) were down-regulated, suggesting that reduced uterine expression of these genes is associated with RIF. Gene Set Enrichment analyses (GSEA) for mRNA microarrays revealed that various signaling pathways including Leukemia inhibitory factor (LIF) signaling and a P4 response were dysregulated in RIFE although expression levels of Estrogen receptor α (ERα) and Progesterone receptor (PR) were not significantly altered in RIFE. Furthermore, expression and phosphorylation of Signal transducer and activator of transcription 3 (STAT3) are reduced and a gene set associated with Janus kinase (JAK)-STAT signaling pathway is systemically down-regulated in these patients. Pairwise analyses of microRNA arrays with prediction of dysregulated microRNAs based on mRNA expression datasets demonstrated that 6 microRNAs are aberrantly regulated in RIFE. Collectively, we here suggest

  10. Integrative Analyses of Uterine Transcriptome and MicroRNAome Reveal Compromised LIF-STAT3 Signaling and Progesterone Response in the Endometrium of Patients with Recurrent/Repeated Implantation Failure (RIF)

    PubMed Central

    Lim, Eun Jin; Park, Miseon; Yoon, Jung Ah; Kim, Yeon Sun; Kim, Eun-Kyung; Shin, Ji-Eun; Kim, Ji Hyang; Kwon, Hwang; Song, Haengseok; Choi, Dong-Hee

    2016-01-01

    Intimate two-way interactions between the implantation-competent blastocyst and receptive uterus are prerequisite for successful embryo implantation. In humans, recurrent/repeated implantation failure (RIF) may occur due to altered uterine receptivity with aberrant gene expression in the endometrium as well as genetic defects in embryos. Several studies have been performed to understand dynamic changes of uterine transcriptome during menstrual cycles in humans. However, uterine transcriptome of the patients with RIF has not been clearly investigated yet. Here we show that several signaling pathways as well as many genes and microRNAs are dysregulated in the endometrium of patients with RIF (RIFE). Whereas unsupervised hierarchical clustering showed that overall mRNA and microRNA profiles of RIFE were similar to those of endometria of healthy women, many genes were significantly dysregulated in RIFE (cut off at 1.5 fold change). The majority (~75%) of differentially expressed genes in RIFE including S100 calcium binding protein P (S100P), Chemokine (C-X-C motif) ligand 13 (CXCL13) and SIX homeobox 1 (SIX1) were down-regulated, suggesting that reduced uterine expression of these genes is associated with RIF. Gene Set Enrichment analyses (GSEA) for mRNA microarrays revealed that various signaling pathways including Leukemia inhibitory factor (LIF) signaling and a P4 response were dysregulated in RIFE although expression levels of Estrogen receptor α (ERα) and Progesterone receptor (PR) were not significantly altered in RIFE. Furthermore, expression and phosphorylation of Signal transducer and activator of transcription 3 (STAT3) are reduced and a gene set associated with Janus kinase (JAK)-STAT signaling pathway is systemically down-regulated in these patients. Pairwise analyses of microRNA arrays with prediction of dysregulated microRNAs based on mRNA expression datasets demonstrated that 6 microRNAs are aberrantly regulated in RIFE. Collectively, we here suggest

  11. Signal analysis applications of nonlinear dynamics and higher-order statistics

    NASA Astrophysics Data System (ADS)

    Solinsky, James C.; Feeney, John J.

    1994-03-01

    The use of higher-order statistics (HOS) in acoustic, and financial signal analysis applications is outlined in theory and followed with specific data examples. HOS analysis is used to identify data regions of interest, and nonlinear dynamics (ND) analysis is used in a 4D embedded space to show structural density changes resulting from the HOS regions. A second-order statistical comparison is made with the same data processed to have random Fourier phase, since the HOS information is contained in this nonrandom phase. These empirical results indicate that HOS data regions are structural distortions to a second-order planar disk in the 4D ND analysis space.

  12. Research of time discrimination circuits for PMT signal readout over large dynamic range in LHAASO WCDA

    NASA Astrophysics Data System (ADS)

    Ma, C.; Zhao, L.; Dong, R.; Jiang, Z.; Chu, S.; Gao, X.; Liu, S.; An, Q.

    2016-11-01

    In the readout electronics of the Water Cerenkov Detector Array (WCDA) in the Large High Altitude Air Shower Observatory (LHAASO), both high-resolution charge and time measurement are required over a dynamic range from 1 photoelectron (P.E.) to 4000 P.E. for the PMT signal readout. In this paper, we present our work on the design of time discrimination circuits in LHAASO WCDA, especially on improvement to reduce the circuit dead time. Several approaches were studied through analysis and simulations, and actual circuits were designed and tested in the laboratory to evaluate the performance. Test results indicate that a time resolution better than 500 ps RMS is achieved in the whole large dynamic range, and the circuit dead time is successfully reduced to less than 200 ns.

  13. Complex oscillatory redox dynamics with signaling potential at the edge between normal and pathological mitochondrial function

    PubMed Central

    Kembro, Jackelyn M.; Cortassa, Sonia; Aon, Miguel A.

    2014-01-01

    The time-keeping properties bestowed by oscillatory behavior on functional rhythms represent an evolutionarily conserved trait in living systems. Mitochondrial networks function as timekeepers maximizing energetic output while tuning reactive oxygen species (ROS) within physiological levels compatible with signaling. In this work, we explore the potential for timekeeping functions dependent on mitochondrial dynamics with the validated two-compartment mitochondrial energetic-redox (ME-R) computational model, that takes into account (a) four main redox couples [NADH, NADPH, GSH, Trx(SH)2], (b) scavenging systems (glutathione, thioredoxin, SOD, catalase) distributed in matrix and extra-matrix compartments, and (c) transport of ROS species between them. Herein, we describe that the ME-R model can exhibit highly complex oscillatory dynamics in energetic/redox variables and ROS species, consisting of at least five frequencies with modulated amplitudes and period according to power spectral analysis. By stability analysis we describe that the extent of steady state—as against complex oscillatory behavior—was dependent upon the abundance of Mn and Cu, Zn SODs, and their interplay with ROS production in the respiratory chain. Large parametric regions corresponding to oscillatory dynamics of increasingly complex waveforms were obtained at low Cu, Zn SOD concentration as a function of Mn SOD. This oscillatory domain was greatly reduced at higher levels of Cu, Zn SOD. Interestingly, the realm of complex oscillations was located at the edge between normal and pathological mitochondrial energetic behavior, and was characterized by oxidative stress. We conclude that complex oscillatory dynamics could represent a frequency- and amplitude-modulated H2O2 signaling mechanism that arises under intense oxidative stress. By modulating SOD, cells could have evolved an adaptive compromise between relative constancy and the flexibility required under stressful redox

  14. Noise-driven signal transmission device using molecular dynamics of organic polymers

    NASA Astrophysics Data System (ADS)

    Asakawa, Naoki; Umemura, Koichiro; Fujise, Shinya; Yazawa, Koji; Shimizu, Tadashi; Tansho, Masataka; Kanki, Teruo; Tanaka, Hidekazu

    2014-01-01

    Stochastic threshold devices using a trap-filling transition (TFT) coupled with molecular dynamics in poly(3-alkylthiophene)s were fabricated as potential key devices for noise-driven bioinspired sensors and information processors. This article deals with variable-temperature direct current conductivity and alternating current impedance measurements for vertical-type device elements of Au/regioregular poly(3-decylthiophene) ((RR-P3DT) (thickness: 100 nm)/Au, which show multiple conducting states and quasi-stochastic transitions between these states. Noise measurements indicate the ω-2-type (if VVTFT) power spectral densities, where V and VTFT are an applied voltage and the voltage for TFT, respectively. The noise generation is due to the TFT associated with twist dynamics of π-conjugated polymers near the order-disorder phase transition (ODT). At 298 K, the quasi-stochastic behavior is more noticeable for RR-P3DT than poly(3-hexylthiophene). The quasi-stochastic property is employed to a stochastic one-directional signal transmitting device using optical-electric conversion. The dynamics of ODT for powder samples were also investigated by differential scanning calorimetry measurements and high-resolution solid-state C13 nuclear magnetic resonance spectroscopy, and the correlation of the molecular structure and dynamics with electric properties was discussed.

  15. Profiling the Dynamics of a Human Phosphorylome Reveals New Components in HGF/c-Met Signaling

    PubMed Central

    Wan, Jun; Xia, Shuli; Newman, Robert; Hu, Jianfei; Zhang, Jin; Hayward, S. Diane; Qian, Jiang; Laterra, John; Zhu, Heng

    2013-01-01

    Protein phosphorylation is a dynamic and reversible event that greatly influences cellular function. Identifying the key regulatory elements that determine cellular phenotypes during development and oncogenesis requires the ability to dynamically monitor proteome-wide events. Here, we report the development of a new strategy to monitor dynamic changes of protein phosphorylation in cells and tissues using functional protein microarrays as the readout. To demonstrate this technology's ability to identify condition-dependent phosphorylation events, human protein microarrays were incubated with lysates from cells or tissues under activation or inhibition of c-Met, a receptor tyrosine kinase involved in tissue morphogenesis and malignancy. By comparing the differences between the protein phosphorylation profiles obtained using the protein microarrays, we were able to recover many of the proteins that are known to be specifically activated (i.e., phosphorylated) upon c-Met activation by the hepatocyte growth factor (HGF). Most importantly, we discovered many proteins that were differentially phosphorylated by lysates from cells or tissues when the c-Met pathway was active. Using phosphorylation-specific antibodies, we were able to validate several candidate proteins as new downstream components of the c-Met signaling pathway in cells. We envision that this new approach, like its DNA microarray counterpart, can be further extended toward profiling dynamics of global protein phosphorylation under many different physiological conditions both in cellulo and in vivo in a high-throughput and cost-effective fashion. PMID:24023761

  16. A new measurement method for the dynamic resistance signal during the resistance spot welding process

    NASA Astrophysics Data System (ADS)

    Wang, Lijing; Hou, Yanyan; Zhang, Hongjie; Zhao, Jian; Xi, Tao; Qi, Xiangyang; Li, Yafeng

    2016-09-01

    To measure the dynamic resistance signal during the resistance spot welding process, some original work was carried out and a new measurement method was developed. Compared with the traditional method, using the instantaneous electrode voltage and welding current at peak current point in each half cycle, the resistance curve from the newly proposed method can provide more details of the dynamic resistance changes over time. To test the specific performance of the proposed method, a series of welding experiments were carried out and the tensile shear strengths of the weld samples were measured. Then, the measurement error of the proposed method was evaluated. Several features were extracted from the dynamic resistance curves. The correlations between the extracted features and weld strength were analyzed and the results show that these features are closely related to the weld strength and they can be used for welding quality monitoring. Moreover, the dynamic resistance curve from the newly proposed method can also be used to monitor some abnormal welding conditions.

  17. I. Advances in NMR Signal Processing. II. Spin Dynamics in Quantum Dissipative Systems

    SciTech Connect

    Lin, Yung-Ya

    1998-11-01

    Part I. Advances in IVMR Signal Processing. Improvements of sensitivity and resolution are two major objects in the development of NMR/MRI. A signal enhancement method is first presented which recovers signal from noise by a judicious combination of a priordmowledge to define the desired feasible solutions and a set theoretic estimation for restoring signal properties that have been lost due to noise contamination. The effect of noise can be significantly mitigated through the process of iteratively modifying the noisy data set to the smallest degree necessary so that it possesses a collection of prescribed properties and also lies closest to the original data set. A novel detection-estimation scheme is then introduced to analyze noisy and/or strongly damped or truncated FIDs. Based on exponential modeling, the number of signals is detected based on information estimated using the matrix pencil method. theory and the spectral parameters are Part II. Spin Dynamics in body dipole-coupled systems Quantum Dissipative Systems. Spin dynamics in manyconstitutes one of the most fundamental problems in magnetic resonance and condensed-matter physics. Its many-spin nature precludes any rigorous treatment. ‘Therefore, the spin-boson model is adopted to describe in the rotating frame the influence of the dipolar local fields on a tagged spin. Based on the polaronic transform and a perturbation treatment, an analytical solution is derived, suggesting the existence of self-trapped states in the. strong coupling limit, i.e., when transverse local field >> longitudinal local field. Such nonlinear phenomena originate from the joint action of the lattice fluctuations and the reaction field. Under semiclassical approximation, it is found that the main effect of the reaction field is the renormalization of the Hamiltonian of interest. Its direct consequence is the two-step relaxation process: the spin is initially localized in a quasiequilibrium state, which is later detrapped by

  18. Dynamic mass redistribution analysis of endogenous β-adrenergic receptor signaling in neonatal rat cardiac fibroblasts.

    PubMed

    Carter, Rhonda L; Grisanti, Laurel A; Yu, Justine E; Repas, Ashley A; Woodall, Meryl; Ibetti, Jessica; Koch, Walter J; Jacobson, Marlene A; Tilley, Douglas G

    2014-02-01

    Label-free systems for the agnostic assessment of cellular responses to receptor stimulation have been shown to provide a sensitive method to dissect receptor signaling. β-adenergic receptors (βAR) are important regulators of normal and pathologic cardiac function and are expressed in cardiomyocytes as well as cardiac fibroblasts, where relatively fewer studies have explored their signaling responses. Using label-free whole cell dynamic mass redistribution (DMR) assays we investigated the response patterns to stimulation of endogenous βAR in primary neonatal rat cardiac fibroblasts (NRCF). Catecholamine stimulation of the cells induced a negative DMR deflection resulting in a concentration-dependent pharmacological response that was competitively blocked by βAR blockade and non-competitively blocked by irreversible uncoupling of Gs proteins. Pharmacological profiling of subtype-selective βAR agonists and antagonists revealed a dominant role of β2AR in mediating the DMR responses, consistent with the relative expression levels of β2AR and β1AR in NRCF. Additionally, βAR-mediated cAMP generation was assessed via a fluorescence biosensor, revealing similar kinetics between DMR responses and cAMP generation. As such, βAR-dependent DMR responses were enhanced via inhibition of cAMP degradation, as well as dynamin-mediated receptor internalization. Finally, we assessed G protein-independent βAR signaling through epidermal growth factor receptor (EGFR). While inhibition of EGFR reduced the DMR response to βAR stimulation, our results demonstrate that G protein-dependent signaling produces a majority of the biological response to βAR stimulation in NRCF. Altogether, measurement of DMR responses in primary cardiac fibroblasts provides a sensitive readout for investigating endogenous βAR signaling via both G protein-dependent and -independent pathways.

  19. Data-driven reverse engineering of signaling pathways using ensembles of dynamic models.

    PubMed

    Henriques, David; Villaverde, Alejandro F; Rocha, Miguel; Saez-Rodriguez, Julio; Banga, Julio R

    2017-02-01

    Despite significant efforts and remarkable progress, the inference of signaling networks from experimental data remains very challenging. The problem is particularly difficult when the objective is to obtain a dynamic model capable of predicting the effect of novel perturbations not considered during model training. The problem is ill-posed due to the nonlinear nature of these systems, the fact that only a fraction of the involved proteins and their post-translational modifications can be measured, and limitations on the technologies used for growing cells in vitro, perturbing them, and measuring their variations. As a consequence, there is a pervasive lack of identifiability. To overcome these issues, we present a methodology called SELDOM (enSEmbLe of Dynamic lOgic-based Models), which builds an ensemble of logic-based dynamic models, trains them to experimental data, and combines their individual simulations into an ensemble prediction. It also includes a model reduction step to prune spurious interactions and mitigate overfitting. SELDOM is a data-driven method, in the sense that it does not require any prior knowledge of the system: the interaction networks that act as scaffolds for the dynamic models are inferred from data using mutual information. We have tested SELDOM on a number of experimental and in silico signal transduction case-studies, including the recent HPN-DREAM breast cancer challenge. We found that its performance is highly competitive compared to state-of-the-art methods for the purpose of recovering network topology. More importantly, the utility of SELDOM goes beyond basic network inference (i.e. uncovering static interaction networks): it builds dynamic (based on ordinary differential equation) models, which can be used for mechanistic interpretations and reliable dynamic predictions in new experimental conditions (i.e. not used in the training). For this task, SELDOM's ensemble prediction is not only consistently better than predictions

  20. Data-driven reverse engineering of signaling pathways using ensembles of dynamic models

    PubMed Central

    Henriques, David; Villaverde, Alejandro F.; Banga, Julio R.

    2017-01-01

    Despite significant efforts and remarkable progress, the inference of signaling networks from experimental data remains very challenging. The problem is particularly difficult when the objective is to obtain a dynamic model capable of predicting the effect of novel perturbations not considered during model training. The problem is ill-posed due to the nonlinear nature of these systems, the fact that only a fraction of the involved proteins and their post-translational modifications can be measured, and limitations on the technologies used for growing cells in vitro, perturbing them, and measuring their variations. As a consequence, there is a pervasive lack of identifiability. To overcome these issues, we present a methodology called SELDOM (enSEmbLe of Dynamic lOgic-based Models), which builds an ensemble of logic-based dynamic models, trains them to experimental data, and combines their individual simulations into an ensemble prediction. It also includes a model reduction step to prune spurious interactions and mitigate overfitting. SELDOM is a data-driven method, in the sense that it does not require any prior knowledge of the system: the interaction networks that act as scaffolds for the dynamic models are inferred from data using mutual information. We have tested SELDOM on a number of experimental and in silico signal transduction case-studies, including the recent HPN-DREAM breast cancer challenge. We found that its performance is highly competitive compared to state-of-the-art methods for the purpose of recovering network topology. More importantly, the utility of SELDOM goes beyond basic network inference (i.e. uncovering static interaction networks): it builds dynamic (based on ordinary differential equation) models, which can be used for mechanistic interpretations and reliable dynamic predictions in new experimental conditions (i.e. not used in the training). For this task, SELDOM’s ensemble prediction is not only consistently better than predictions

  1. Glycerol Monolaurate (GML) inhibits human T cell signaling and function by disrupting lipid dynamics

    PubMed Central

    Zhang, Michael S.; Sandouk, Aline; Houtman, Jon C. D.

    2016-01-01

    Glycerol Monolaurate (GML) is a naturally occurring fatty acid widely utilized in food, cosmetics, and homeopathic supplements. GML is a potent antimicrobial agent that targets a range of bacteria, fungi, and enveloped viruses but select findings suggest that GML also has immunomodulatory functions. In this study, we have mechanistically examined if GML affects the signaling and functional output of human primary T cells. We found that GML potently altered order and disorder dynamics in the plasma membrane that resulted in reduced formation of LAT, PLC-γ, and AKT microclusters. Altered membrane events induced selective inhibition of TCR-induced phosphorylation of regulatory P85 subunit of PI3K and AKT as well as abrogated calcium influx. Ultimately, GML treatment potently reduced TCR-induced production of IL-2, IFN-γ, TNF-α, and IL-10. Our data reveal that the widely used anti-microbial agent GML also alters the lipid dynamics of human T cells, leading to their defective signaling and function. PMID:27456316

  2. Conformational Dynamics in FKBP Domains: Relevance to Molecular Signaling and Drug Design.

    PubMed

    LeMaster, David M; Hernandez, Griselda

    2015-01-01

    Among the 22 FKBP domains in the human genome, FKBP12.6 and the first FKBP domains (FK1) of FKBP51 and FKBP52 are evolutionarily and structurally most similar to the archetypical FKBP12. As such, the development of inhibitors with selectivity among these four FKBP domains poses a significant challenge for structure-based design. The pleiotropic effects of these FKBP domains in a range of signaling processes such as the regulation of ryanodine receptor calcium channels by FKBP12 and FKBP12.6 and steroid receptor regulation by the FK1 domains of FKBP51 and FKBP52 amply justify the efforts to develop selective therapies. In contrast to their close structural similarities, these four FKBP domains exhibit a substantial diversity in their conformational flexibility. A number of distinct conformational transitions have been characterized for FKBP12 spanning timeframes from 20 s to 10 ns and in each case these dynamics have been shown to markedly differ from the conformational behavior for one or more of the other three FKBP domains. Protein flexibilitybased inhibitor design could draw upon the transitions that are significantly populated in only one of the targeted proteins. Both the similarities and differences among these four proteins valuably inform the understanding of how dynamical effects propagate across the FKBP domains as well as potentially how such intramolecular transitions might couple to the larger scale transitions that are central to the signaling complexes in which these FKBP domains function.

  3. Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms

    PubMed Central

    Cohen, Michael; Kicheva, Anna; Ribeiro, Ana; Blassberg, Robert; Page, Karen M.; Barnes, Chris P.; Briscoe, James

    2015-01-01

    In the vertebrate neural tube, the morphogen Sonic Hedgehog (Shh) establishes a characteristic pattern of gene expression. Here we quantify the Shh gradient in the developing mouse neural tube and show that while the amplitude of the gradient increases over time, the activity of the pathway transcriptional effectors, Gli proteins, initially increases but later decreases. Computational analysis of the pathway suggests three mechanisms that could contribute to this adaptation: transcriptional upregulation of the inhibitory receptor Ptch1, transcriptional downregulation of Gli and the differential stability of active and inactive Gli isoforms. Consistent with this, Gli2 protein expression is downregulated during neural tube patterning and adaptation continues when the pathway is stimulated downstream of Ptch1. Moreover, the Shh-induced upregulation of Gli2 transcription prevents Gli activity levels from adapting in a different cell type, NIH3T3 fibroblasts, despite the upregulation of Ptch1. Multiple mechanisms therefore contribute to the intracellular dynamics of Shh signalling, resulting in different signalling dynamics in different cell types. PMID:25833741

  4. Comparison of Dynamical Behaviors Between Monofunctional and Bifunctional Two-Component Signaling Modules

    NASA Astrophysics Data System (ADS)

    Yang, Xiyan; Wu, Yahao; Yuan, Zhanjiang

    2015-06-01

    Two-component signaling modules exist extensively in bacteria and microbes. These modules can be, based on their distinct network structures, divided into two types: the monofunctional system (denoted by MFS) where the sensor kinase (SK) modulates only phosphorylation of the response regulator (RR), and the bifunctional system (denoted by BFS) where the SK catalyzes both phosphorylation and dephosphorylation of the RR. Here, we analyze dynamical behaviors of these two systems based on stability theory, focusing on differences between them. The analysis of the deterministic behavior indicates that there is no difference between the two modules, that is, each system has the unique stable steady state. However, there are significant differences in stochastic behavior between them. Specifically, if the mean phosphorylated SK level is kept the same for the two modules, then the variance and the Fano factor for the phosphorylated RR in the BFS are always no less than those in the MFS, indicating that bifunctionality always enhances fluctuations. The correlation between the phosphorylated SK and the phosphorylated RR in the BFS is always positive mainly due to competition between system components, but this correlation in the MFS may be positive, almost zero, or negative, depending on the ratio between two rate constants. Our overall analysis indicates that differences between dynamical behaviors of monofunctional and bifunctional signaling modules are mainly in the stochastic rather than deterministic aspect.

  5. Dynamic crystallography reveals early signalling events in ultraviolet photoreceptor UVR8

    DOE PAGES

    Zeng, Xiaoli; Ren, Zhong; Wu, Qi; ...

    2015-01-08

    Arabidopsis thaliana UVR8 (AtUVR8) is a long-sought-after photoreceptor that undergoes dimer dissociation in response to UV-B light. Crystallographic and mutational studies have identified two crucial tryptophan residues for UV-B responses in AtUVR8. However, the mechanism of UV-B perception and structural events leading up to dimer dissociation remain elusive at the molecular level. We applied dynamic crystallography to capture light-induced structural events in photoactive AtUVR8 crystals. Here we report two intermediate structures at 1.67Å resolution. At the epicenter of UV-B signaling, concerted motions associated with Trp285/Trp233 lead to ejection of a water molecule, which weakens an intricate network of hydrogen bondsmore » and salt bridges at the dimer interface. Partial opening of the β-propeller structure due to thermal relaxation of conformational strains originating in the epicenter further disrupts the dimer interface and leads to dimer dissociation. Ultimately, these dynamic crystallographic observations provide structural insights into the photo-perception and signaling mechanism of UVR8.« less

  6. Dynamic crystallography reveals early signalling events in ultraviolet photoreceptor UVR8

    SciTech Connect

    Zeng, Xiaoli; Ren, Zhong; Wu, Qi; Fan, Jun; Peng, Pan -Pan; Tang, Kun; Zhang, Ruiqin; Zhao, Kai -Hong; Yang, Xiaojing

    2015-01-08

    Arabidopsis thaliana UVR8 (AtUVR8) is a long-sought-after photoreceptor that undergoes dimer dissociation in response to UV-B light. Crystallographic and mutational studies have identified two crucial tryptophan residues for UV-B responses in AtUVR8. However, the mechanism of UV-B perception and structural events leading up to dimer dissociation remain elusive at the molecular level. We applied dynamic crystallography to capture light-induced structural events in photoactive AtUVR8 crystals. Here we report two intermediate structures at 1.67Å resolution. At the epicenter of UV-B signaling, concerted motions associated with Trp285/Trp233 lead to ejection of a water molecule, which weakens an intricate network of hydrogen bonds and salt bridges at the dimer interface. Partial opening of the β-propeller structure due to thermal relaxation of conformational strains originating in the epicenter further disrupts the dimer interface and leads to dimer dissociation. Ultimately, these dynamic crystallographic observations provide structural insights into the photo-perception and signaling mechanism of UVR8.

  7. Scale-Free and Multifractal Time Dynamics of fMRI Signals during Rest and Task

    PubMed Central

    Ciuciu, P.; Varoquaux, G.; Abry, P.; Sadaghiani, S.; Kleinschmidt, A.

    2012-01-01

    Scaling temporal dynamics in functional MRI (fMRI) signals have been evidenced for a decade as intrinsic characteristics of ongoing brain activity (Zarahn et al., 1997). Recently, scaling properties were shown to fluctuate across brain networks and to be modulated between rest and task (He, 2011): notably, Hurst exponent, quantifying long memory, decreases under task in activating and deactivating brain regions. In most cases, such results were obtained: First, from univariate (voxelwise or regionwise) analysis, hence focusing on specific cognitive systems such as Resting-State Networks (RSNs) and raising the issue of the specificity of this scale-free dynamics modulation in RSNs. Second, using analysis tools designed to measure a single scaling exponent related to the second order statistics of the data, thus relying on models that either implicitly or explicitly assume Gaussianity and (asymptotic) self-similarity, while fMRI signals may significantly depart from those either of those two assumptions (Ciuciu et al., 2008; Wink et al., 2008). To address these issues, the present contribution elaborates on the analysis of the scaling properties of fMRI temporal dynamics by proposing two significant variations. First, scaling properties are technically investigated using the recently introduced Wavelet Leader-based Multifractal formalism (WLMF; Wendt et al., 2007). This measures a collection of scaling exponents, thus enables a richer and more versatile description of scale invariance (beyond correlation and Gaussianity), referred to as multifractality. Also, it benefits from improved estimation performance compared to tools previously used in the literature. Second, scaling properties are investigated in both RSN and non-RSN structures (e.g., artifacts), at a broader spatial scale than the voxel one, using a multivariate approach, namely the Multi-Subject Dictionary Learning (MSDL) algorithm (Varoquaux et al., 2011) that produces a set of spatial components that

  8. Dynamic receptor team formation can explain the high signal transduction gain in Escherichia coli.

    PubMed

    Albert, Réka; Chiu, Yu-Wen; Othmer, Hans G

    2004-05-01

    Evolution has provided many organisms with sophisticated sensory systems that enable them to respond to signals in their environment. The response frequently involves alteration in the pattern of movement, either by directed movement, a process called taxis, or by altering the speed or frequency of turning, which is called kinesis. Chemokinesis has been most thoroughly studied in the peritrichous bacterium Escherichia coli, which has four helical flagella distributed over the cell surface, and swims by rotating them. When rotated counterclockwise the flagella coalesce into a propulsive bundle, producing a relatively straight "run," and when rotated clockwise they fly apart, resulting in a "tumble" which reorients the cell with little translocation. A stochastic process generates the runs and tumbles, and in a chemoeffector gradient, runs that carry the cell in a favorable direction are extended. The cell senses spatial gradients as temporal changes in receptor occupancy and changes the probability of counterclockwise rotation (the bias) on a fast timescale, but adaptation returns the bias to baseline on a slow timescale, enabling the cell to detect and respond to further concentration changes. The overall structure of the signal transduction pathways is well characterized in E. coli, but important details are still not understood. Only recently has a source of gain in the signal transduction network been identified experimentally, and here we present a mathematical model based on dynamic assembly of receptor teams that can explain this observation.

  9. Analysis and compensation for code Doppler effect of BDS II signal under high dynamics

    NASA Astrophysics Data System (ADS)

    Ouyang, Xiaofeng; Zeng, Fangling

    2016-01-01

    In high dynamic circumstances, the acquisition of BDS (BeiDou Navigation Satellite System) signal would be affected by the pseudo-code Doppler. The pseudo-code frequency shift is more prominent and complex when BOC modulation has been adopted by BDS-II, but is not yet involved in current compensation algorithm. In addition, the most frequently used code Doppler compensation algorithm is modifying the sampling rate or local bit rate, which not only increases the complexity of the acquisition and tracking, but also is barely realizable for the hardware receiver to modify the local frequency. Therefore, this paper proposes a code Doppler compensation method based on double estimator receiver, which simultaneously controls NCO delay of code tracking loop and subcarrier tracking loop to compensate for pseudo-code frequency shift. The simulation and test are implemented with BDS-II BOC signal. The test results demonstrate that the proposed algorithm can effectively compensate for pseudo-code Doppler of BOC signal and has detection probability 3dB higher than the uncompensated situation when the false alarm rate is under 0.01 and the coherent integration time is 1ms.

  10. Dynamic Receptor Team Formation Can Explain the High Signal Transduction Gain in Escherichia coli

    PubMed Central

    Albert, Réka; Chiu, Yu-wen; Othmer, Hans G.

    2004-01-01

    Evolution has provided many organisms with sophisticated sensory systems that enable them to respond to signals in their environment. The response frequently involves alteration in the pattern of movement, either by directed movement, a process called taxis, or by altering the speed or frequency of turning, which is called kinesis. Chemokinesis has been most thoroughly studied in the peritrichous bacterium Escherichia coli, which has four helical flagella distributed over the cell surface, and swims by rotating them. When rotated counterclockwise the flagella coalesce into a propulsive bundle, producing a relatively straight “run,” and when rotated clockwise they fly apart, resulting in a “tumble” which reorients the cell with little translocation. A stochastic process generates the runs and tumbles, and in a chemoeffector gradient, runs that carry the cell in a favorable direction are extended. The cell senses spatial gradients as temporal changes in receptor occupancy and changes the probability of counterclockwise rotation (the bias) on a fast timescale, but adaptation returns the bias to baseline on a slow timescale, enabling the cell to detect and respond to further concentration changes. The overall structure of the signal transduction pathways is well characterized in E. coli, but important details are still not understood. Only recently has a source of gain in the signal transduction network been identified experimentally, and here we present a mathematical model based on dynamic assembly of receptor teams that can explain this observation. PMID:15111386

  11. Structural insights into the dynamic process of β2-adrenergic receptor signaling

    PubMed Central

    Manglik, Aashish; Kim, Tae Hun; Masureel, Matthieu; Altenbach, Christian; Yang, Zhongyu; Hilger, Daniel; Lerch, Michael T.; Kobilka, Tong Sun; Thian, Foon Sun; Hubbell, Wayne L.; Prosser, R. Scott; Kobilka, Brian K.

    2015-01-01

    SUMMARY G protein-coupled receptors (GPCRs) transduce signals from the extracellular environment to intracellular proteins. To gain structural insight into the regulation of receptor cytoplasmic conformations by extracellular ligands during signaling, we examine the structural dynamics of the cytoplasmic domain of the β2-adrenergic receptor (β2AR) using 19F-fluorine NMR and double electron-electron resonance spectroscopy. These studies show that unliganded and inverse-agonist-bound β2AR exists predominantly in two inactive conformations that exchange within hundreds of microseconds. Although agonists shift the equilibrium towards a conformation capable of engaging cytoplasmic G proteins, they do so incompletely, resulting in increased conformational heterogeneity and the coexistence of inactive, intermediate and active states. Complete transition to the active conformation requires subsequent interaction with a G-protein or an intracellular G protein mimetic. These studies demonstrate a loose allosteric coupling of the agonist-binding site and G protein-coupling interface that may generally be responsible for the complex signaling behavior observed for many GPCRs. PMID:25981665

  12. The auxin signalling network translates dynamic input into robust patterning at the shoot apex

    PubMed Central

    Vernoux, Teva; Brunoud, Géraldine; Farcot, Etienne; Morin, Valérie; Van den Daele, Hilde; Legrand, Jonathan; Oliva, Marina; Das, Pradeep; Larrieu, Antoine; Wells, Darren; Guédon, Yann; Armitage, Lynne; Picard, Franck; Guyomarc'h, Soazig; Cellier, Coralie; Parry, Geraint; Koumproglou, Rachil; Doonan, John H; Estelle, Mark; Godin, Christophe; Kepinski, Stefan; Bennett, Malcolm; De Veylder, Lieven; Traas, Jan

    2011-01-01

    The plant hormone auxin is thought to provide positional information for patterning during development. It is still unclear, however, precisely how auxin is distributed across tissues and how the hormone is sensed in space and time. The control of gene expression in response to auxin involves a complex network of over 50 potentially interacting transcriptional activators and repressors, the auxin response factors (ARFs) and Aux/IAAs. Here, we perform a large-scale analysis of the Aux/IAA-ARF pathway in the shoot apex of Arabidopsis, where dynamic auxin-based patterning controls organogenesis. A comprehensive expression map and full interactome uncovered an unexpectedly simple distribution and structure of this pathway in the shoot apex. A mathematical model of the Aux/IAA-ARF network predicted a strong buffering capacity along with spatial differences in auxin sensitivity. We then tested and confirmed these predictions using a novel auxin signalling sensor that reports input into the signalling pathway, in conjunction with the published DR5 transcriptional output reporter. Our results provide evidence that the auxin signalling network is essential to create robust patterns at the shoot apex. PMID:21734647

  13. Balanced ionotropic receptor dynamics support signal estimation via voltage-dependent membrane noise.

    PubMed

    Marcoux, Curtis M; Clarke, Stephen E; Nesse, William H; Longtin, Andre; Maler, Leonard

    2016-01-01

    Encoding behaviorally relevant stimuli in a noisy background is critical for animals to survive in their natural environment. We identify core biophysical and synaptic mechanisms that permit the encoding of low-frequency signals in pyramidal neurons of the weakly electric fish Apteronotus leptorhynchus, an animal that can accurately encode even miniscule amplitude modulations of its self-generated electric field. We demonstrate that slow NMDA receptor (NMDA-R)-mediated excitatory postsynaptic potentials (EPSPs) are able to summate over many interspike intervals (ISIs) of the primary electrosensory afferents (EAs), effectively eliminating the baseline EA ISI correlations from the pyramidal cell input. Together with a dynamic balance of NMDA-R and GABA-A-R currents, this permits stimulus-evoked changes in EA spiking to be transmitted efficiently to target electrosensory lobe (ELL) pyramidal cells, for encoding low-frequency signals. Interestingly, AMPA-R activity is depressed and appears to play a negligible role in the generation of action potentials. Instead, we hypothesize that cell-intrinsic voltage-dependent membrane noise supports the encoding of perithreshold sensory input; this noise drives a significant proportion of pyramidal cell spikes. Together, these mechanisms may be sufficient for the ELL to encode signals near the threshold of behavioral detection.

  14. Reliable emotion recognition system based on dynamic adaptive fusion of forehead biopotentials and physiological signals.

    PubMed

    Khezri, Mahdi; Firoozabadi, Mohammad; Sharafat, Ahmad Reza

    2015-11-01

    In this study, we proposed a new adaptive method for fusing multiple emotional modalities to improve the performance of the emotion recognition system. Three-channel forehead biosignals along with peripheral physiological measurements (blood volume pressure, skin conductance, and interbeat intervals) were utilized as emotional modalities. Six basic emotions, i.e., anger, sadness, fear, disgust, happiness, and surprise were elicited by displaying preselected video clips for each of the 25 participants in the experiment; the physiological signals were collected simultaneously. In our multimodal emotion recognition system, recorded signals with the formation of several classification units identified the emotions independently. Then the results were fused using the adaptive weighted linear model to produce the final result. Each classification unit is assigned a weight that is determined dynamically by considering the performance of the units during the testing phase and the training phase results. This dynamic weighting scheme enables the emotion recognition system to adapt itself to each new user. The results showed that the suggested method outperformed conventional fusion of the features and classification units using the majority voting method. In addition, a considerable improvement, compared to the systems that used the static weighting schemes for fusing classification units, was also shown. Using support vector machine (SVM) and k-nearest neighbors (KNN) classifiers, the overall classification accuracies of 84.7% and 80% were obtained in identifying the emotions, respectively. In addition, applying the forehead or physiological signals in the proposed scheme indicates that designing a reliable emotion recognition system is feasible without the need for additional emotional modalities.

  15. Understanding Dynamic Patterns of NF-κB Signaling: Derivation and Analysis of a Minimal Model through Sensitivity Analysis

    NASA Astrophysics Data System (ADS)

    Joo, Jaewook; Plimpton, Steve; Martin, Shawn; Swiler, Laura; Faulon, Jean-Loup

    2007-03-01

    Understanding the pleiotropism of NF-κB signal transduction is a challenge of clear medical importance and systems biology. Current mathematical modeling frameworks for NF-κB signal transduction, though limited to a small signaling module located in a downstream of IKK, heavily rely on the parameterizations and the numerical studies of ODE models and doubtless lack intuitive explanations about underlying mechanisms of the dynamic patterns of the NF-κB signaling. Here we present a systematic way to derive a minimal model from an up-to-dated and detailed NF-κB signaling network by means of sensitivity analysis. Using analysis of the minimal model, we predict a dose-response curve shape, existence of Hopf-bifurcation, and underlying mechanisms of all possible dynamic patterns of NF-κB signaling. Simulating the detailed ODE model for NF-κB signaling network with large sets of the parameter values that are sampled from the biologically feasible parameter space, we present an ensemble of all possible dynamic patterns of NF-κB signaling and verify the predictions from the minimal model.

  16. Investigation of Rhodopsin Dynamics in its Signaling State by Solid-State Deuterium NMR Spectroscopy

    PubMed Central

    Struts, Andrey V.; Chawla, Udeep; Perera, Suchithranga M.D.C.; Brown, Michael F.

    2017-01-01

    Site-directed deuterium NMR spectroscopy is a valuable tool to study the structural dynamics of biomolecules in cases where solution NMR is inapplicable. Solid-state 2H NMR spectral studies of aligned membrane samples of rhodopsin with selectively labeled retinal provide information on structural changes of the chromophore in different protein states. In addition, solid-state 2H NMR relaxation time measurements allow one to study the dynamics of the ligand during the transition from the inactive to the active state. Here we describe the methodological aspects of solid-state 2H NMR spectroscopy for functional studies of rhodopsin, with an emphasis on the dynamics of the retinal cofactor. We provide complete protocols for the preparation of NMR samples of rhodopsin with 11-cis-retinal selectively deuterated at the methyl groups in aligned membranes. In addition, we review optimized conditions for trapping the rhodopsin photointermediates; and lastly we address the challenging problem of trapping the signaling state of rhodopsin in aligned membrane films. PMID:25697522

  17. MicroRNA roles in signalling during lactation: an insight from differential expression, time course and pathway analyses of deep sequence data

    PubMed Central

    Do, Duy N.; Li, Ran; Dudemaine, Pier-Luc; Ibeagha-Awemu, Eveline M.

    2017-01-01

    The study examined microRNA (miRNA) expression and regulatory patterns during an entire bovine lactation cycle. Total RNA from milk fat samples collected at the lactogenesis (LAC, day1 [D1] and D7), galactopoiesis (GAL, D30, D70, D130, D170 and D230) and involution (INV, D290 and when milk production dropped to 5 kg/day) stages from 9 cows was used for miRNA sequencing. A total of 475 known and 238 novel miRNAs were identified. Fifteen abundantly expressed miRNAs across lactation stages play regulatory roles in basic metabolic, cellular and immunological functions. About 344, 366 and 209 miRNAs were significantly differentially expressed (DE) between GAL and LAC, INV and GAL, and INV and LAC stages, respectively. MiR-29b/miR-363 and miR-874/miR-6254 are important mediators for transition signals from LAC to GAL and from GAL to INV, respectively. Moreover, 58 miRNAs were dynamically DE in all lactation stages and 19 miRNAs were significantly time-dependently DE throughout lactation. Relevant signalling pathways for transition between lactation stages are involved in apoptosis (PTEN and SAPK/JNK), intracellular signalling (protein kinase A, TGF-β and ERK5), cell cycle regulation (STAT3), cytokines, hormones and growth factors (prolactin, growth hormone and glucocorticoid receptor). Overall, our data suggest diverse, temporal and physiological signal-dependent regulatory and mediator functions for miRNAs during lactation. PMID:28317898

  18. Color signal encoding for high dynamic range and wide color gamut based on human perception

    NASA Astrophysics Data System (ADS)

    Nezamabadi, Mahdi; Miller, Scott; Daly, Scott; Atkins, Robin

    2014-01-01

    A new EOTF based on human perception, called PQ (Perceptual Quantizer), was proposed in a previous work (SMPTE Mot. Imag. J 2013, 122:52-59) and its performance was evaluated for a wide range of luminance levels and encoding bitdepth values. This paper is an extension of that previous work to include the color aspects of the PQ signal encoding. The efficiency of the PQ encoding and bit-depth requirements were evaluated and compared for standard color gamuts of Rec 709 (SRGB), and the wide color gamuts of Rec 2020, P3, and ACES for a variety of signal representations as RGB, YCbCr, and XYZ. In a selected color space for any potential local gray level 26 color samples were simulated by deviating one quantization step from the original color in each signal dimension. The quantization step sizes were simulated based on the PQ and gamma curves for different bit-depth values and luminance ranges for each of the color gamut spaces and signal representations. Color differences between the gray field and the simulated color samples were computed using CIE DE2000 color difference equation. The maximum color difference values (quantization error) were used as a metric to evaluate the performance of the corresponding EOTF curve. Extended color gamuts were found to require more bits to maintain low quantization error. Extended dynamic range required fewer additional bits in to maintain quantization error. Regarding the visual detection thresholds, the minimum bit-depth required by the PQ and gamma encodings are evaluated and compared through visual experiments.

  19. Wavelet Analyses and Applications

    ERIC Educational Resources Information Center

    Bordeianu, Cristian C.; Landau, Rubin H.; Paez, Manuel J.

    2009-01-01

    It is shown how a modern extension of Fourier analysis known as wavelet analysis is applied to signals containing multiscale information. First, a continuous wavelet transform is used to analyse the spectrum of a nonstationary signal (one whose form changes in time). The spectral analysis of such a signal gives the strength of the signal in each…

  20. Population dynamics and genetic changes of Picea abies in the South Carpathians revealed by pollen and ancient DNA analyses

    PubMed Central

    2011-01-01

    Background Studies on allele length polymorphism designate several glacial refugia for Norway spruce (Picea abies) in the South Carpathian Mountains, but infer only limited expansion from these refugia after the last glaciation. To better understand the genetic dynamics of a South Carpathian spruce lineage, we compared ancient DNA from 10,700 and 11,000-year-old spruce pollen and macrofossils retrieved from Holocene lake sediment in the Retezat Mountains with DNA extracted from extant material from the same site. We used eight primer pairs that amplified short and variable regions of the spruce cpDNA. In addition, from the same lake sediment we obtained a 15,000-years-long pollen accumulation rate (PAR) record for spruce that helped us to infer changes in population size at this site. Results We obtained successful amplifications for Norway spruce from 17 out of 462 pollen grains tested, while the macrofossil material provided 22 DNA sequences. Two fossil sequences were found to be unique to the ancient material. Population genetic statistics showed higher genetic diversity in the ancient individuals compared to the extant ones. Similarly, statistically significant Ks and Kst values showed a considerable level of differentiation between extant and ancient populations at the same loci. Lateglacial and Holocene PAR values suggested that population size of the ancient population was small, in the range of 1/10 or 1/5 of the extant population. PAR analysis also detected two periods of rapid population growths (from ca. 11,100 and 3900 calibrated years before present (cal yr BP)) and three bottlenecks (around 9180, 7200 and 2200 cal yr BP), likely triggered by climatic change and human impact. Conclusion Our results suggest that the paternal lineages observed today in the Retezat Mountains persisted at this site at least since the early Holocene. Combination of the results from the genetic and the PAR analyses furthermore suggests that the higher level of genetic

  1. Analyses of Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics Pre and Post Short and Long-Duration Space Flights

    NASA Technical Reports Server (NTRS)

    Alperin, Noam; Barr, Yael; Lee, Sang H.; Mason,Sara; Bagci, Ahmet M.

    2015-01-01

    Preliminary results are based on analyses of data from 17 crewmembers. The initial analysis compares pre to post-flight changes in total cerebral blood flow (CBF) and craniospinal CSF flow volume. Total CBF is obtained by summation of the mean flow rates through the 4 blood vessels supplying the brain (right and left internal carotid and vertebral arteries). Volumetric flow rates were obtained using an automated lumen segmentation technique shown to have 3-4-fold improved reproducibility and accuracy over manual lumen segmentation (6). Two cohorts, 5 short-duration and 8 long-duration crewmembers, who were scanned within 3 to 8 days post landing were included (4 short-duration crewmembers with MRI scans occurring beyond 10 days post flight were excluded). The VIIP Clinical Practice Guideline (CPG) classification is being used initially as a measure for VIIP syndrome severity. Median CPG scores of the short and long-duration cohorts were similar, 2. Mean preflight total CBF for the short and long-duration cohorts were similar, 863+/-144 and 747+/-119 mL/min, respectively. Percentage CBF changes for all short duration crewmembers were 11% or lower, within the range of normal physiological fluctuations in healthy individuals. In contrast, in 4 of the 8 long-duration crewmembers, the change in CBF exceeded the range of normal physiological fluctuation. In 3 of the 4 subjects an increase in CBF was measured. Large pre to post-flight changes in the craniospinal CSF flow volume were found in 6 of the 8 long-duration crewmembers. Box-Whisker plots of the CPG and the percent CBF and CSF flow changes for the two cohorts are shown in Figure 4. Examples of CSF flow waveforms for a short and two long-duration (CPG 0 and 3) are shown in Figure 5. Changes in CBF and CSF flow dynamics larger than normal physiological fluctuations were observed in the long-duration crewmembers. Changes in CSF flow were more pronounced than changes in CBF. Decreased CSF flow dynamics were observed

  2. Signal classification using global dynamical models, Part II: SONAR data analysis

    SciTech Connect

    Kremliovsky, M.; Kadtke, J.

    1996-06-01

    In Part I of this paper, we described a numerical method for nonlinear signal detection and classification which made use of techniques borrowed from dynamical systems theory. Here in Part II of the paper, we will describe an example of data analysis using this method, for data consisting of open ocean acoustic (SONAR) recordings of marine mammal transients, supplied from NUWC sources. The purpose here is two-fold: first to give a more operational description of the technique and provide rules-of-thumb for parameter choices; and second to discuss some new issues raised by the analysis of non-ideal (real-world) data sets. The particular data set considered here is quite non-stationary, relatively noisy, is not clearly localized in the background, and as such provides a difficult challenge for most detection/classification schemes. {copyright} {ital 1996 American Institute of Physics.}

  3. Single-Cell Migration in Complex Microenvironments: Mechanics and Signaling Dynamics

    PubMed Central

    Mak, Michael; Spill, Fabian; Kamm, Roger D.; Zaman, Muhammad H.

    2016-01-01

    Cells are highly dynamic and mechanical automata powered by molecular motors that respond to external cues. Intracellular signaling pathways, either chemical or mechanical, can be activated and spatially coordinated to induce polarized cell states and directional migration. Physiologically, cells navigate through complex microenvironments, typically in three-dimensional (3D) fibrillar networks. In diseases, such as metastatic cancer, they invade across physiological barriers and remodel their local environments through force, matrix degradation, synthesis, and reorganization. Important external factors such as dimensionality, confinement, topographical cues, stiffness, and flow impact the behavior of migrating cells and can each regulate motility. Here, we review recent progress in our understanding of single-cell migration in complex microenvironments. PMID:26639083

  4. Emerging roles of tRNA in adaptive translation, signalling dynamics and disease.

    PubMed

    Kirchner, Sebastian; Ignatova, Zoya

    2015-02-01

    tRNAs, nexus molecules between mRNAs and proteins, have a central role in translation. Recent discoveries have revealed unprecedented complexity of tRNA biosynthesis, modification patterns, regulation and function. In this Review, we present emerging concepts regarding how tRNA abundance is dynamically regulated and how tRNAs (and their nucleolytic fragments) are centrally involved in stress signalling and adaptive translation, operating across a wide range of timescales. Mutations in tRNAs or in genes affecting tRNA biogenesis are also linked to complex human diseases with surprising heterogeneity in tissue vulnerability, and we highlight cell-specific aspects that modulate the disease penetrance of tRNA-based pathologies.

  5. Signal classification using global dynamical models, Part II: SONAR data analysis

    NASA Astrophysics Data System (ADS)

    Kremliovsky, Michael; Kadtke, James

    1996-06-01

    In Part I of this paper, we described a numerical method for nonlinear signal detection and classification which made use of techniques borrowed from dynamical systems theory. Here in Part II of the paper, we will describe an example of data analysis using this method, for data consisting of open ocean acoustic (SONAR) recordings of marine mammal transients, supplied from NUWC sources. The purpose here is two-fold: first to give a more operational description of the technique and provide rules-of-thumb for parameter choices; and second to discuss some new issues raised by the analysis of non-ideal (real-world) data sets. The particular data set considered here is quite non-stationary, relatively noisy, is not clearly localized in the background, and as such provides a difficult challenge for most detection/classification schemes.

  6. Detection, Evaluation, and Optimization of Optical Signals Generated by Fiber Optic Bragg Gratings Under Dynamic Excitations

    NASA Technical Reports Server (NTRS)

    Adamovsky, Grigory; Lekki, John; Lock, James A.

    2002-01-01

    The dynamic response of a fiber optic Bragg grating to mechanical vibrations is examined both theoretically and experimentally. The theoretical expressions describing the consequences of changes in the grating's reflection spectrum are derived for partially coherent beams in an interferometer. The analysis is given in terms of the dominant wavelength, optical bandwidth, and optical path difference of the interfering signals. Changes in the reflection spectrum caused by a periodic stretching and compression of the grating were experimentally measured using an unbalanced Michelson interferometer, a Michelson interferometer with a non-zero optical path difference. The interferometer's sensitivity to changes in dominant wavelength of the interfering beams was measured as a function of interferometer unbalance and was compared to theoretical predictions. The theoretical analysis enables the user to determine the optimum performance for an unbalanced interferometer.

  7. The dynamics of Rho GTPase signaling and implications for targeting cancer and the tumor microenvironment

    PubMed Central

    Pajic, Marina; Herrmann, David; Vennin, Claire; Conway, James RW; Chin, Venessa T; Johnsson, Anna-Karin E; Welch, Heidi CE; Timpson, Paul

    2015-01-01

    Numerous large scale genomics studies have demonstrated that cancer is a molecularly heterogeneous disease, characterized by acquired changes in the structure and DNA sequence of tumor genomes. More recently, the role of the equally complex tumor microenvironment in driving the aggressiveness of this disease is increasingly being realized. Tumor cells are surrounded by activated stroma, creating a dynamic environment that promotes cancer development, metastasis and chemoresistance. The Rho family of small GTPases plays an essential role in the regulation of cell shape, cytokinesis, cell adhesion, and cell motility. Importantly, these processes need to be considered in the context of a complex 3-dimensional (3D) environment, with reciprocal feedback and cross-talk taking place between the tumor cells and host environment. Here we discuss the role of molecular networks involving Rho GTPases in cancer, and the therapeutic implications of inhibiting Rho signaling in both cancer cells and the emerging concept of targeting the surrounding stroma. PMID:26103062

  8. Novel pseudo-wavelet function for MMG signal extraction during dynamic fatiguing contractions.

    PubMed

    Al-Mulla, Mohammed Rashid; Sepulveda, Francisco

    2014-05-28

    The purpose of this study was to develop an algorithm to classify muscle fatigue content in sports related scenarios. Mechanomyography (MMG) signals of the biceps muscle were recorded from thirteen subjects performing dynamic contractions until fatigue. For training and testing purposes, the signals were labeled in two classes (Non-Fatigue and Fatigue). A genetic algorithm was used to evolve a pseudo-wavelet function for optimizing the detection of muscle fatigue. Tuning of the generalized evolved pseudo-wavelet function was based on the decomposition of 70% of the conducted MMG trials. After completing 25 independent pseudo-wavelet evolution runs, the best run was selected and then tested on the remaining 30% of the data to measure the classification performance. Results show that the evolved pseudo-wavelet improved the classification rate of muscle fatigue by 4.70 percentage points to 16.61 percentage points when compared to other standard wavelet functions, giving an average correct classification of 80.63%, with statistical significance (p < 0.05).

  9. Network dynamics determine the autocrine and paracrine signaling functions of TNF

    PubMed Central

    Caldwell, Andrew B.; Cheng, Zhang; Vargas, Jesse D.; Birnbaum, Harry A.

    2014-01-01

    A hallmark of the inflammatory response to pathogen exposure is the production of tumor necrosis factor (TNF) that coordinates innate and adaptive immune responses by functioning in an autocrine or paracrine manner. Numerous molecular mechanisms contributing to TNF production have been identified, but how they function together in macrophages remains unclear. Here, we pursued an iterative systems biology approach to develop a quantitative understanding of the regulatory modules that control TNF mRNA synthesis and processing, mRNA half-life and translation, and protein processing and secretion. By linking the resulting model of TNF production to models of the TLR-, the TNFR-, and the NFκB signaling modules, we were able to study TNF’s functions during the inflammatory response to diverse TLR agonists. Contrary to expectation, we predicted and then experimentally confirmed that in response to lipopolysaccaride, TNF does not have an autocrine function in amplifying the NFκB response, although it plays a potent paracrine role in neighboring cells. However, in response to CpG DNA, autocrine TNF extends the duration of NFκB activity and shapes CpG-induced gene expression programs. Our systems biology approach revealed that network dynamics of MyD88 and TRIF signaling and of cytokine production and response govern the stimulus-specific autocrine and paracrine functions of TNF. PMID:25274725

  10. Novel Pseudo-Wavelet Function for MMG Signal Extraction during Dynamic Fatiguing Contractions

    PubMed Central

    Al-Mulla, Mohamed R.; Sepulveda, Francisco

    2014-01-01

    The purpose of this study was to develop an algorithm to classify muscle fatigue content in sports related scenarios. Mechanomyography (MMG) signals of the biceps muscle were recorded from thirteen subjects performing dynamic contractions until fatigue. For training and testing purposes, the signals were labeled in two classes (Non-Fatigue and Fatigue). A genetic algorithm was used to evolve a pseudo-wavelet function for optimizing the detection of muscle fatigue. Tuning of the generalized evolved pseudo-wavelet function was based on the decomposition of 70% of the conducted MMG trials. After completing 25 independent pseudo-wavelet evolution runs, the best run was selected and then tested on the remaining 30% of the data to measure the classification performance. Results show that the evolved pseudo-wavelet improved the classification rate of muscle fatigue by 4.70 percentage points to 16.61 percentage points when compared to other standard wavelet functions, giving an average correct classification of 80.63%, with statistical significance (p < 0.05). PMID:24878591

  11. Signal-to-noise analysis of cerebral blood volume maps from dynamic NMR imaging studies.

    PubMed

    Boxerman, J L; Rosen, B R; Weisskoff, R M

    1997-01-01

    The use of cerebral blood volume (CBV) maps generated from dynamic MRI studies tracking the bolus passage of paramagnetic contrast agents strongly depends on the signal-to-noise ratio (SNR) of the maps. The authors present a semianalytic model for the noise in CBV maps and introduce analytic and Monte Carlo techniques for determining the effect of experimental parameters and processing strategies upon CBV-SNR. CBV-SNR increases as more points are used to estimate the baseline signal level. For typical injections, maps made with 10 baseline points have 34% more noise than those made with 50 baseline points. For a given peak percentage signal drop, an optimum TE can be chosen that, in general, is less than the baseline T2. However, because CBV-SNR is relatively insensitive to TE around this optimum value, choosing TE approximately equal to T2 does not sacrifice much SNR for typical doses of contrast agent. The TR that maximizes spin-echo CBV-SNR satisfies TR/T1 approximately equal to 1.26, whereas as short a TR as possible should be used to maximize gradient-echo CBV-SNR. In general, CBV-SNR is maximized for a given dose of contrast agent by selecting as short an input bolus duration as possible. For image SNR exceeding 20-30, the gamma-fitting procedure adds little extra noise compared with simple numeric integration. However, for noisier input images, can be the case for high resolution echo-planar images, the covarying parameters of the gamma-variate fit broaden the distribution of the CBV estimate and thereby decrease CBV-SNR. The authors compared the analytic noise predicted by their model with that of actual patient data and found that the analytic model accounts for roughly 70% of the measured variability of CBV within white matter regions of interest.

  12. Adaptive Kalman filtering methods for tracking GPS signals in high noise/high dynamic environments

    NASA Astrophysics Data System (ADS)

    Zuo, Qiyao; Yuan, Hong; Lin, Baojun

    2007-11-01

    GPS C/A signal tracking algorithms have been developed based on adaptive Kalman filtering theory. In the research, an adaptive Kalman filter is used to substitute for standard tracking loop filters. The goal is to improve estimation accuracy and tracking stabilization in high noise and high dynamic environments. The linear dynamics model and the measurements model are designed to estimate code phase, carrier phase, Doppler shift, and rate of change of Doppler shift. Two adaptive algorithms are applied to improve robustness and adaptive faculty of the tracking, one is Sage adaptive filtering approach and the other is strong tracking method. Both the new algorithms and the conventional tracking loop have been tested by using simulation data. In the simulation experiment, the highest jerk of the receiver is set to 10G m/s 3 with the lowest C/No 30dBHz. The results indicate that the Kalman filtering algorithms are more robust than the standard tracking loop, and performance of tracking loop using the algorithms is satisfactory in such extremely adverse circumstances.

  13. Changes in actin dynamics are involved in salicylic acid signaling pathway.

    PubMed

    Matoušková, Jindřiška; Janda, Martin; Fišer, Radovan; Sašek, Vladimír; Kocourková, Daniela; Burketová, Lenka; Dušková, Jiřina; Martinec, Jan; Valentová, Olga

    2014-06-01

    Changes in actin cytoskeleton dynamics are one of the crucial players in many physiological as well as non-physiological processes in plant cells. Positioning of actin filament arrays is necessary for successful establishment of primary lines of defense toward pathogen attack, depolymerization leads very often to the enhanced susceptibility to the invading pathogen. On the other hand it was also shown that the disruption of actin cytoskeleton leads to the induction of defense response leading to the expression of PATHOGENESIS RELATED proteins (PR). In this study we show that pharmacological actin depolymerization leads to the specific induction of genes in salicylic acid pathway but not that involved in jasmonic acid signaling. Life imaging of leafs of Arabidopsis thaliana with GFP-tagged fimbrin (GFP-fABD2) treated with 1 mM salicylic acid revealed rapid disruption of actin filaments resembling the pattern viewed after treatment with 200 nM latrunculin B. The effect of salicylic acid on actin filament fragmentation was prevented by exogenous addition of phosphatidic acid, which binds to the capping protein and thus promotes actin polymerization. The quantitative evaluation of actin filament dynamics is also presented.

  14. Systematic parameter estimation in data-rich environments for cell signalling dynamics

    PubMed Central

    Nim, Tri Hieu; Luo, Le; Clément, Marie-Véronique; White, Jacob K.; Tucker-Kellogg, Lisa

    2013-01-01

    Motivation: Computational models of biological signalling networks, based on ordinary differential equations (ODEs), have generated many insights into cellular dynamics, but the model-building process typically requires estimating rate parameters based on experimentally observed concentrations. New proteomic methods can measure concentrations for all molecular species in a pathway; this creates a new opportunity to decompose the optimization of rate parameters. Results: In contrast with conventional parameter estimation methods that minimize the disagreement between simulated and observed concentrations, the SPEDRE method fits spline curves through observed concentration points, estimates derivatives and then matches the derivatives to the production and consumption of each species. This reformulation of the problem permits an extreme decomposition of the high-dimensional optimization into a product of low-dimensional factors, each factor enforcing the equality of one ODE at one time slice. Coarsely discretized solutions to the factors can be computed systematically. Then the discrete solutions are combined using loopy belief propagation, and refined using local optimization. SPEDRE has unique asymptotic behaviour with runtime polynomial in the number of molecules and timepoints, but exponential in the degree of the biochemical network. SPEDRE performance is comparatively evaluated on a novel model of Akt activation dynamics including redox-mediated inactivation of PTEN (phosphatase and tensin homologue). Availability and implementation: Web service, software and supplementary information are available at www.LtkLab.org/SPEDRE Supplementary information: Supplementary data are available at Bioinformatics online. Contact: LisaTK@nus.edu.sg PMID:23426255

  15. Analysis of Wnt signalling dynamics during colon crypt development in 3D culture

    PubMed Central

    Tan, Chin Wee; Hirokawa, Yumiko; Burgess, Antony W.

    2015-01-01

    Many systems biology studies lack context-relevant data and as a consequence the predictive capabilities can be limited in developing targeted cancer therapeutics. Production of colon crypt in vitro is ideal for studying colon systems biology. This report presents the first production of, to our knowledge, physiologically-shaped, functional colon crypts in vitro (i.e. single crypts with cells expressing Mucin 2 and Chromogranin A). Time-lapsed monitoring of crypt formation revealed an increased frequency of single-crypt formation in the absence of noggin. Using quantitative 3D immunofluorescence of β-catenin and E-cadherin, spatial-temporal dynamics of these proteins in normal colon crypt cells stimulated with Wnt3A or inhibited by cycloheximide has been measured. Colon adenoma cultures established from APCmin/+ mouse have developmental differences and β-catenin spatial localization compared to normal crypts. Quantitative data describing the effects of signalling pathways and proteins dynamics for both normal and adenomatous colon crypts is now within reach to inform a systems approach to colon crypt biology. PMID:26087250

  16. Clustering in Cell Cycle Dynamics with General Response/Signaling Feedback

    PubMed Central

    Young, Todd R.; Fernandez, Bastien; Buckalew, Richard; Moses, Gregory; Boczko, Erik M.

    2011-01-01

    Motivated by experimental and theoretical work on autonomous oscillations in yeast, we analyze ordinary differential equations models of large populations of cells with cell-cycle dependent feedback. We assume a particular type of feedback that we call Responsive/Signaling (RS), but do not specify a functional form of the feedback. We study the dynamics and emergent behaviour of solutions, particularly temporal clustering and stability of clustered solutions. We establish the existence of certain periodic clustered solutions as well as “uniform” solutions and add to the evidence that cell-cycle dependent feedback robustly leads to cell-cycle clustering. We highlight the fundamental differences in dynamics between systems with negative and positive feedback. For positive feedback systems the most important mechanism seems to be the stability of individual isolated clusters. On the other hand we find that in negative feedback systems, clusters must interact with each other to reinforce coherence. We conclude from various details of the mathematical analysis that negative feedback is most consistent with observations in yeast experiments. PMID:22001733

  17. Long-Range Signaling in MutS and MSH Homologs via Switching of Dynamic Communication Pathways

    PubMed Central

    Wang, Beibei; Francis, Joshua; Law, Sean M.; Feig, Michael

    2016-01-01

    Allostery is conformation regulation by propagating a signal from one site to another distal site. This study focuses on the long-range communication in DNA mismatch repair proteins MutS and its homologs where intramolecular signaling has to travel over 70 Å to couple lesion detection to ATPase activity and eventual downstream repair. Using dynamic network analysis based on extensive molecular dynamics simulations, multiple preserved communication pathways were identified that would allow such long-range signaling. The pathways appear to depend on the nucleotides bound to the ATPase domain as well as the type of DNA substrate consistent with previously proposed functional cycles of mismatch recognition and repair initiation by MutS and homologs. A mechanism is proposed where pathways are switched without major conformational rearrangements allowing for efficient long-range signaling and allostery. PMID:27768684

  18. A feedback control system for real-time formant estimation. I--Static and dynamic analysis for sinusoidal input signals.

    PubMed

    Zierhofer, C M; Hochmair, E S

    1993-09-01

    This paper presents a novel analog scheme suitable for the real-time estimation of formant frequencies. Formant tracking is based on a feedback technique which uses both the amplitude and phase characteristics of two stagger-tuned bandpass filters to give an improved dynamic behavior. The implementation of the system requires a small number of components, and is practical for low-power applications. An analysis of the static and dynamic behavior is given for sinusoidal input signals. The transient response is independent of the amplitude level of the input signal. The system is designed for second formant detection in a cochlear prosthesis system.

  19. Temporal dynamics in an immunological synapse: Role of thermal fluctuations in signaling

    NASA Astrophysics Data System (ADS)

    Bush, Daniel R.; Chattopadhyay, Amit K.

    2015-07-01

    The article analyzes the contribution of stochastic thermal fluctuations in the attachment times of the immature T-cell receptor TCR: peptide-major-histocompatibility-complex pMHC immunological synapse bond. The key question addressed here is the following: how does a synapse bond remain stabilized in the presence of high-frequency thermal noise that potentially equates to a strong detaching force? Focusing on the average time persistence of an immature synapse, we show that the high-frequency nodes accompanying large fluctuations are counterbalanced by low-frequency nodes that evolve over longer time periods, eventually leading to signaling of the immunological synapse bond primarily decided by nodes of the latter type. Our analysis shows that such a counterintuitive behavior could be easily explained from the fact that the survival probability distribution is governed by two distinct phases, corresponding to two separate time exponents, for the two different time regimes. The relatively shorter timescales correspond to the cohesion:adhesion induced immature bond formation whereas the larger time reciprocates the association:dissociation regime leading to TCR:pMHC signaling. From an estimate of the bond survival probability, we show that, at shorter timescales, this probability PΔ(τ ) scales with time τ as a universal function of a rescaled noise amplitude D/Δ2, such that PΔ(τ ) ˜τ-(Δ/√{D }+1/2 ) ,Δ being the distance from the mean intermembrane (T cell:Antigen Presenting Cell) separation distance. The crossover from this shorter to a longer time regime leads to a universality in the dynamics, at which point the survival probability shows a different power-law scaling compared to the one at shorter timescales. In biological terms, such a crossover indicates that the TCR:pMHC bond has a survival probability with a slower decay rate than the longer LFA-1:ICAM-1 bond justifying its stability.

  20. Programmable retinal dynamics in a CMOS mixed-signal array processor chip

    NASA Astrophysics Data System (ADS)

    Carmona, Ricardo A.; Jimenez-Garrido, Francisco J.; Dominguez-Castro, Rafael; Espejo, Servando; Rodriguez-Vazquez, Angel

    2003-04-01

    The retina is responsible of the treatment of visual information at early stages. Visual stimuli generate patterns of activity that are transmitted through its layered structure up to the ganglion cells that interface it to the optical nerve. In this trip of micrometers, information is sustained by continuous signals that interact in excitatory and inhibitory ways. This low-level processing compresses the relevant information of the images to a manageable size. The behavior of the more external layers of the biological retina has been successfully modelled within the Cellular Neural Network framework. Interactions between cells are realized on a local basic. Each cell interacts with its nearest neighbors and every cell in the same layer follows the same interconnection pattern. Intra- and inter-layer interactions are continuous in magnitude and time. The evolution of the network can be described by a set of coupled nonlinear differential equations. A mixed-signal VLSI implementation of focal-plane low-level image processing based upon this biological model constitutes a feasible and cost effective alternative to conventional digital processing in real-time applications. A CMOS Programmable Array Processor prototype chip has been designed and fabricated in a standard technology. It has been successfully tested, validating the proposed design techniques. The integrated system consists of a network of 2 coupled layers, containing 32×32 elementary processors, running at different time constants. Involved image processing algorithms can be programmed on this chip by tuning the appropriate interconnection weights, internally coded as analog but programmed via a digital interface. Propagative, active wave phenomena and retina-lake effects can be observed in this chip. Low-level image processing tasks for early vision applications can be developed based on these high-order dynamics.

  1. Dynamics of β-adrenergic/cAMP signaling and morphological changes in cultured astrocytes.

    PubMed

    Vardjan, Nina; Kreft, Marko; Zorec, Robert

    2014-04-01

    The morphology of astrocytes, likely regulated by cAMP, determines the structural association between astrocytes and the synapse, consequently modulating synaptic function. β-Adrenergic receptors (β-AR), which increase cytosolic cAMP concentration ([cAMP]i ), may affect cell morphology. However, the real-time dynamics of β-AR-mediated cAMP signaling in single live astrocytes and its effect on cell morphology have not been studied. We used the fluorescence resonance energy transfer (FRET)-based cAMP biosensor Epac1-camps to study time-dependent changes in [cAMP]i ; morphological changes in primary rat astrocytes were monitored by real-time confocal microscopy. Stimulation of β-AR by adrenaline, noradrenaline, and isoprenaline, a specific agonist of β-AR, rapidly increased [cAMP]i (∼15 s). The FRET signal response, mediated via β-AR, was faster than in the presence of forskolin (twofold) and dibutyryl-cAMP (>35-fold), which directly activate adenylyl cyclase and Epac1-camps, respectively, likely due to slow entry of these agents into the cytosol. Oscillations in [cAMP]i have not been recorded, indicating that cAMP-dependent processes operate in a slow time domain. Most Epac1-camps expressing astrocytes revealed a morphological change upon β-AR activation and attained a stellate morphology within 1 h. The morphological changes exhibited a bell-shaped dependency on [cAMP]i . The 5-10% decrease in cell cross-sectional area and the 30-50% increase in cell perimeter are likely due to withdrawal of the cytoplasm to the perinuclear region and the appearance of protrusions on the surface of astrocytes. Because astrocyte processes ensheath neurons, β-AR/cAMP-mediated morphological changes can modify the geometry of the extracellular space, affecting synaptic, neuronal, and astrocyte functions in health and disease.

  2. Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions.

    PubMed

    Halldorsdottir, Valgerdur G; Dave, Jaydev K; Leodore, Lauren M; Eisenbrey, John R; Park, Suhyun; Hall, Anne L; Thomenius, Kai; Forsberg, Flemming

    2011-07-01

    Our group has proposed the concept of subharmonic aided pressure estimation (SHAPE) utilizing microbubble-based ultrasound contrast agent signals for the noninvasive estimation of hydrostatic blood pressures. An experimental system for in vitro SHAPE was constructed based on two single-element transducers assembled confocally at a 60 degree angle to each other. Changes in the first, second and subharmonic amplitudes of five different ultrasound contrast agents were measured in vitro at static hydrostatic pressures from 0-186 mmHg, acoustic pressures from 0.35-0.60 MPa peak-to-peak and frequencies of 2.5-6.6 MHz. The most sensitive agent and optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI). This implementation of SHAPE was then tested under dynamic-flow conditions and compared to pressure-catheter measurements. Over the pressure range studied, the first and second harmonic amplitudes reduced approximately 2 dB for all contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 9-14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r = 0.98, p < 0.001). Optimal sensitivity was achieved at a transmit frequency of 2.5 MHz and acoustic pressure of 0.35 MPa using Sonazoid (GE Healthcare, Oslo, Norway). A Logiq 9 scanner was modified to implement SHAPE on a convex transducer with a frequency range from 1.5-4.5 MHz and acoustic pressures from 0-3.34 MPa. Results matched the pressure catheter (r2 = 0.87). In conclusion, subharmonic contrast signals are a good indicator of hydrostatic pressure. Out of the five ultrasound contrast agents tested, Sonazoid was the most sensitive for subharmonic pressure estimation. Real-time SHAPE has been implemented on a commercial scanner and offers the possibility of allowing pressures in the heart and elsewhere to be obtained noninvasively.

  3. On protection of Freedom's solar dynamic radiator from the orbital debris environment. Part 2: Further testing and analyses

    NASA Technical Reports Server (NTRS)

    Rhatigan, Jennifer L.; Christiansen, Eric L.; Fleming, Michael L.

    1991-01-01

    Presented here are results of a test program undertaken to further define the response of the solar dynamic radiator to hypervelocity impact (HVI). Tests were conducted on representative radiator panels (under ambient, nonoperating conditions) over a range of velocity. Target parameters are also varied. Data indicate that analytical penetration predictions are conservative (i.e., pessimistic) for the specific configuration of the solar dynamic radiator. Test results are used to define the solar dynamic radiator reliability with respect to HVI more rigorously than previous studies. Test data, reliability, and survivability results are presented.

  4. CXCL13/CXCR5 signaling enhances BCR-triggered B-cell activation by shaping cell dynamics.

    PubMed

    Sáez de Guinoa, Julia; Barrio, Laura; Mellado, Mario; Carrasco, Yolanda R

    2011-08-11

    Continuous migration of B cells at the follicle contrasts with their stable arrest after encounter with antigen. Two main ligand/receptor pairs are involved in these cell behaviors: the chemokine CXCL13/chemokine receptor CXCR5 and antigen/BCR. Little is known regarding the interplay between CXCR5 and BCR signaling in the modulation of B-cell dynamics and its effect on B-cell activation. We used a 2-dimensional model to study B-cell migration and antigen recognition in real time, and found that BCR signaling strength alters CXCL13-mediated migration, leading to a heterogeneous B-cell behavior pattern. In addition, we demonstrate that CXCL13/CXCR5 signaling does not impair BCR-triggered immune synapse formation and that CXCR5 is excluded from the central antigen cluster. CXCL13/CXCR5 signaling enhances BCR-mediated B-cell activation in at least 2 ways: (1) it assists antigen gathering at the synapse by promoting membrane ruffling and lymphocyte function-associated antigen 1 (LFA-1)-supported adhesion, and (2) it allows BCR signaling integration in motile B cells through establishment of LFA-1-supported migratory junctions. Both processes require functional actin cytoskeleton and non-muscle myosin II motor protein. Therefore, the CXCL13/CXCR5 signaling effect on shaping B-cell dynamics is an effective mechanism that enhances antigen encounter and BCR-triggered B-cell activation.

  5. RSK2 signals through stathmin to promote microtubule dynamics and tumor metastasis.

    PubMed

    Alesi, G N; Jin, L; Li, D; Magliocca, K R; Kang, Y; Chen, Z G; Shin, D M; Khuri, F R; Kang, S

    2016-10-13

    Metastasis is responsible for >90% of cancer-related deaths. Complex signaling in cancer cells orchestrates the progression from a primary to a metastatic cancer. However, the mechanisms of these cellular changes remain elusive. We previously demonstrated that p90 ribosomal S6 kinase 2 (RSK2) promotes tumor metastasis. Here we investigated the role of RSK2 in the regulation of microtubule dynamics and its potential implication in cancer cell invasion and tumor metastasis. Stable knockdown of RSK2 disrupted microtubule stability and decreased phosphorylation of stathmin, a microtubule-destabilizing protein, at serine 16 in metastatic human cancer cells. We found that RSK2 directly binds and phosphorylates stathmin at the leading edge of cancer cells. Phosphorylation of stathmin by RSK2 reduced stathmin-mediated microtubule depolymerization. Moreover, overexpression of phospho-mimetic mutant stathmin S16D significantly rescued the decreased invasive and metastatic potential mediated by RSK2 knockdown in vitro and in vivo. Furthermore, stathmin phosphorylation positively correlated with RSK2 expression and metastatic cancer progression in primary patient tumor samples. Our finding demonstrates that RSK2 directly phosphorylates stathmin and regulates microtubule polymerization to provide a pro-invasive and pro-metastatic advantage to cancer cells. Therefore, the RSK2-stathmin pathway represents a promising therapeutic target and a prognostic marker for metastatic human cancers.

  6. K(+) regulates Ca(2+) to drive inflammasome signaling: dynamic visualization of ion flux in live cells.

    PubMed

    Yaron, J R; Gangaraju, S; Rao, M Y; Kong, X; Zhang, L; Su, F; Tian, Y; Glenn, H L; Meldrum, D R

    2015-10-29

    P2X7 purinergic receptor engagement with extracellular ATP induces transmembrane potassium and calcium flux resulting in assembly of the NLRP3 inflammasome in LPS-primed macrophages. The role of potassium and calcium in inflammasome regulation is not well understood, largely due to limitations in existing methods for interrogating potassium in real time. The use of KS6, a novel sensor for selective and sensitive dynamic visualization of intracellular potassium flux in live cells, multiplexed with the intracellular calcium sensor Fluo-4, revealed a coordinated relationship between potassium and calcium. Interestingly, the mitochondrial potassium pool was mobilized in a P2X7 signaling, and ATP dose-dependent manner, suggesting a role for mitochondrial sensing of cytosolic ion perturbation. Through treatment with extracellular potassium we found that potassium efflux was necessary to permit sustained calcium entry, but not transient calcium flux from intracellular stores. Further, intracellular calcium chelation with BAPTA-AM indicated that P2X7-induced potassium depletion was independent of calcium mobilization. This evidence suggests that both potassium efflux and calcium influx are necessary for mitochondrial reactive oxygen generation upstream of NLRP3 inflammasome assembly and pyroptotic cell death. We propose a model wherein potassium efflux is necessary for calcium influx, resulting in mitochondrial reactive oxygen generation to trigger the NLRP3 inflammasome.

  7. Dynamics of fMRI signals during human brain activations to a stimulus

    NASA Astrophysics Data System (ADS)

    Liu, Haiying; Kato, Toshinori; Neves, Carlos

    2001-05-01

    In fMRI memory study, the temporal behavior of BOLD fMRI signals were consistently observed from various brain processing areas at 1.5 Tesla and consistent with the expected functions. Also, all the activations generally exhibit three types of temporal characteristics: short, sustained and delayed responses in relation to the primary stimuli. To address these cerebral multiphasic responses, a suitable functional data analysis scheme has been used, in which the neural response of a specific brain area to a pre-determined stimulation input of some sort was assumed to be linear. The visual memory study was performed on 6 normal subjects on a clinical MR scanner using a 5 min long rapid dynamical whole brain imaging using EPI acquisition during a single memory task, which involved a 45 sec visual presentation of three simple abstract geometric figures to the subject via LCD projector. The results showed that the activations in visual cortex were tightly correlated with the visual stimulus, while the activations detected in interior temporal, entorhinal cortex and inferior temporal area were delayed. Using the new technique, the brian activations were further characterized quantitatively in terms of delay and prolonged response. The resulting effective impulse response functions corresponding to these brain activations revealed much clearly all the temporal components.

  8. Detecting scaling in the period dynamics of multimodal signals: Application to Parkinsonian tremor

    NASA Astrophysics Data System (ADS)

    Sapir, Nir; Karasik, Roman; Havlin, Shlomo; Simon, Ely; Hausdorff, Jeffrey M.

    2003-03-01

    Patients with Parkinson’s disease exhibit tremor, involuntary movement of the limbs. The frequency spectrum of tremor typically has broad peaks at “harmonic” frequencies, much like that seen in other physical processes. In general, this type of harmonic structure in the frequency domain may be due to two possible mechanisms: a nonlinear oscillation or a superposition of (multiple) independent modes of oscillation. A broad peak spectrum generally indicates that a signal is semiperiodic with a fluctuating period. These fluctuations may posses intrinsic order that can be quantified using scaling analysis. We propose a method to extract the correlation (scaling) properties in the period dynamics of multimodal oscillations, in order to distinguish between a nonlinear oscillation and a superposition of individual modes of oscillation. The method is based on our finding that the information content of the temporal correlations in a fluctuating period of a single oscillator is contained in a finite frequency band in the power spectrum, allowing for decomposition of modes by bandpass filtering. Our simulations for a nonlinear oscillation show that harmonic modes possess the same scaling properties. In contrast, when the method is applied to tremor records from patients with Parkinson’s disease, the first two modes of oscillations yield different scaling patterns, suggesting that these modes may not be simple harmonics, as might be initially assumed.

  9. Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics.

    PubMed

    Schober, Markus; Raghavan, Srikala; Nikolova, Maria; Polak, Lisa; Pasolli, H Amalia; Beggs, Hilary E; Reichardt, Louis F; Fuchs, Elaine

    2007-02-26

    In response to alphabeta1 integrin signaling, transducers such as focal adhesion kinase (FAK) become activated, relaying to specific machineries and triggering distinct cellular responses. By conditionally ablating Fak in skin epidermis and culturing Fak-null keratinocytes, we show that FAK is dispensable for epidermal adhesion and basement membrane assembly, both of which require alphabeta1 integrins. FAK is also dispensible for proliferation/survival in enriched medium. In contrast, FAK functions downstream of alphabeta1 integrin in regulating cytoskeletal dynamics and orchestrating polarized keratinocyte migration out of epidermal explants. Fak-null keratinocytes display an aberrant actin cytoskeleton, which is tightly associated with robust, peripheral focal adhesions and microtubules. We find that without FAK, Src, p190RhoGAP, and PKL-PIX-PAK, localization and/or activation at focal adhesions are impaired, leading to elevated Rho activity, phosphorylation of myosin light chain kinase, and enhanced tensile stress fibers. We show that, together, these FAK-dependent activities are critical to control the turnover of focal adhesions, which is perturbed in the absence of FAK.

  10. Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans

    PubMed Central

    Kumar, Neeraj; Jagtap, Urmila; Verma, Sonia; Mukhopadhyay, Arnab

    2015-01-01

    Lowering insulin-IGF-1-like signalling (IIS) activates FOXO transcription factors (TF) to extend life span across species. To study the dynamics of FOXO chromatin occupancy under this condition in C. elegans, we report the first recruitment profile of endogenous DAF-16 and show that the response is conserved. DAF-16 predominantly acts as a transcriptional activator and binding within the 0.5 kb promoter-proximal region results in maximum induction of downstream targets that code for proteins involved in detoxification and longevity. Interestingly, genes that are activated under low IIS already have higher DAF-16 recruited to their promoters in WT. DAF-16 binds to variants of the FOXO consensus sequence in the promoter proximal regions of genes that are exclusively targeted during low IIS. We also define a set of ‘core’ direct targets, after comparing multiple studies, which tend to co-express and contribute robustly towards IIS-associated phenotypes. Additionally, we show that nuclear hormone receptor DAF-12 as well as zinc-finger TF EOR-1 may bind DNA in close proximity to DAF-16 and distinct TF classes that are direct targets of DAF-16 may be instrumental in regulating its indirect targets. Together, our study provides fundamental insights into the transcriptional biology of FOXO/DAF-16 and gene regulation downstream of the IIS pathway. PMID:26539642

  11. Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation

    PubMed Central

    Ankers, John M; Awais, Raheela; Jones, Nicholas A; Boyd, James; Ryan, Sheila; Adamson, Antony D; Harper, Claire V; Bridge, Lloyd; Spiller, David G; Jackson, Dean A; Paszek, Pawel; Sée, Violaine; White, Michael RH

    2016-01-01

    Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle. DOI: http://dx.doi.org/10.7554/eLife.10473.001 PMID:27185527

  12. Biomechanical analyses of static and dynamic fixation techniques of retrograde interlocking femoral nailing using nonlinear finite element methods.

    PubMed

    Shih, Kao-Shang; Hsu, Ching-Chi; Hsu, Tzu-Pin; Hou, Sheng-Mou; Liaw, Chen-Kun

    2014-02-01

    Femoral shaft fractures can be treated using retrograde interlocking nailing systems; however, fracture nonunion still occurs. Dynamic fixation techniques, which remove either the proximal or distal locking screws, have been used to solve the problem of nonunion. In addition, a surgical rule for dynamic fixation techniques has been defined based on past clinical reports. However, the biomechanical performance of the retrograde interlocking nailing systems with either the traditional static fixation technique or the dynamic fixation techniques has not been investigated by using nonlinear numerical modeling. Three-dimensional nonlinear finite element models were developed, and the implant strength, fixation stability, and contact area of the fracture surfaces were evaluated. Three types of femoral shaft fractures (a proximal femoral shaft fracture, a middle femoral shaft fracture, and a distal femoral shaft fracture) fixed by three fixation techniques (insertion of all the locking screws, removal of the proximal locking screws, or removal of the distal locking screws) were analyzed. The results showed that the static fixation technique resulted in sufficient fixation stability and that the dynamic fixation techniques decreased the failure risk of the implant and produced a larger contact area of the fracture surfaces. The outcomes of the current study could assist orthopedic surgeons in comprehending the biomechanical performances of both static and dynamic fixation techniques. In addition, the surgeons could also select a fixation technique based on the specific patient situation using the numerical outcomes of this study.

  13. SRM Internal Flow Tests and Computational Fluid Dynamic Analysis. Volume 2; CFD RSRM Full-Scale Analyses

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This document presents the full-scale analyses of the CFD RSRM. The RSRM model was developed with a 20 second burn time. The following are presented as part of the full-scale analyses: (1) RSRM embedded inclusion analysis; (2) RSRM igniter nozzle design analysis; (3) Nozzle Joint 4 erosion anomaly; (4) RSRM full motor port slag accumulation analysis; (5) RSRM motor analysis of two-phase flow in the aft segment/submerged nozzle region; (6) Completion of 3-D Analysis of the hot air nozzle manifold; (7) Bates Motor distributed combustion test case; and (8) Three Dimensional Polysulfide Bump Analysis.

  14. Integrated signaling pathway and gene expression regulatory model to dissect dynamics of Escherichia coli challenged mammary epithelial cells.

    PubMed

    den Breems, Nicoline Y; Nguyen, Lan K; Kulasiri, Don

    2014-12-01

    Cells transform external stimuli, through the activation of signaling pathways, which in turn activate gene regulatory networks, in gene expression. As more omics data are generated from experiments, eliciting the integrated relationship between the external stimuli, the signaling process in the cell and the subsequent gene expression is a major challenge in systems biology. The complex system of non-linear dynamic protein interactions in signaling pathways and gene networks regulates gene expression. The complexity and non-linear aspects have resulted in the study of the signaling pathway or the gene network regulation in isolation. However, this limits the analysis of the interaction between the two components and the identification of the source of the mechanism differentiating the gene expression profiles. Here, we present a study of a model of the combined signaling pathway and gene network to highlight the importance of integrated modeling. Based on the experimental findings we developed a compartmental model and conducted several simulation experiments. The model simulates the mRNA expression of three different cytokines (RANTES, IL8 and TNFα) regulated by the transcription factor NFκB in mammary epithelial cells challenged with E. coli. The analysis of the gene network regulation identifies a lack of robustness and therefore sensitivity for the transcription factor regulation. However, analysis of the integrated signaling and gene network regulation model reveals distinctly different underlying mechanisms in the signaling pathway responsible for the variation between the three cytokine's mRNA expression levels. Our key findings reveal the importance of integrating the signaling pathway and gene expression dynamics in modeling. Modeling infers valid research questions which need to be verified experimentally and can assist in the design of future biological experiments.

  15. The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression.

    PubMed

    Vincan, Elizabeth; Barker, Nick

    2008-01-01

    The constitutive activation of beta-catenin-dependent ('canonical') Wnt signalling is a necessary initiating event in the genesis of most colorectal cancers. As this constitutive activation occurs through genetic mutation of one of the down-stream components of the signalling pathway, it was presumed that additional regulation of beta-catenin-dependent Wnt signalling would be inconsequential. However, it is now recognised that additional modulation of beta-catenin-dependent Wnt signalling is involved in tumour progression, and many of the genes associated with tumour invasion and metastasis are beta-catenin/TCF transcriptional target genes that are dynamically regulated during cancer progression. Intriguingly, the demonstration that naturally occurring inhibitors of Wnt-Frizzled (FZD) interaction are bona fide tumour suppressors in this cancer suggests that additional modulation of Wnt signalling is via the upstream components of the pathway. This is corroborated by recent studies that demonstrate tumour-promoting roles for Wnt and FZD per se. Moreover, both beta-catenin-dependent and beta-catenin-independent Wnt/FZD-mediated signalling is implicated during the dynamic and reversible EMT and MET that underscore colorectal cancer progression. Importantly, therapeutic targeting of the Wnt signalling pathway at the plasma membrane is clearly indicated by the profound anti-tumour activity of small molecule inhibitors and dominant-negative receptor constructs that target the receptor complex. The potential to effectively target EMT and MET processes at the plasma membrane via the upstream components of the Wnt signalling pathway offers new hope for anti-cancer therapy.

  16. Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals

    PubMed Central

    Guo, Yiran; Lanktree, Matthew B.; Taylor, Kira C.; Hakonarson, Hakon; Lange, Leslie A.; Keating, Brendan J.

    2013-01-01

    Recent genetic association studies have made progress in uncovering components of the genetic architecture of the body mass index (BMI). We used the ITMAT-Broad-Candidate Gene Association Resource (CARe) (IBC) array comprising up to 49 320 single nucleotide polymorphisms (SNPs) across ∼2100 metabolic and cardiovascular-related loci to genotype up to 108 912 individuals of European ancestry (EA), African-Americans, Hispanics and East Asians, from 46 studies, to provide additional insight into SNPs underpinning BMI. We used a five-phase study design: Phase I focused on meta-analysis of EA studies providing individual level genotype data; Phase II performed a replication of cohorts providing summary level EA data; Phase III meta-analyzed results from the first two phases; associated SNPs from Phase III were used for replication in Phase IV; finally in Phase V, a multi-ethnic meta-analysis of all samples from four ethnicities was performed. At an array-wide significance (P < 2.40E-06), we identify novel BMI associations in loci translocase of outer mitochondrial membrane 40 homolog (yeast) - apolipoprotein E - apolipoprotein C-I (TOMM40-APOE-APOC1) (rs2075650, P = 2.95E-10), sterol regulatory element binding transcription factor 2 (SREBF2, rs5996074, P = 9.43E-07) and neurotrophic tyrosine kinase, receptor, type 2 [NTRK2, a brain-derived neurotrophic factor (BDNF) receptor gene, rs1211166, P = 1.04E-06] in the Phase IV meta-analysis. Of 10 loci with previous evidence for BMI association represented on the IBC array, eight were replicated, with the remaining two showing nominal significance. Conditional analyses revealed two independent BMI-associated signals in BDNF and melanocortin 4 receptor (MC4R) regions. Of the 11 array-wide significant SNPs, three are associated with gene expression levels in both primary B-cells and monocytes; with rs4788099 in SH2B adaptor protein 1 (SH2B1) notably being associated with the expression of multiple genes in cis. These multi

  17. Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals.

    PubMed

    Guo, Yiran; Lanktree, Matthew B; Taylor, Kira C; Hakonarson, Hakon; Lange, Leslie A; Keating, Brendan J

    2013-01-01

    Recent genetic association studies have made progress in uncovering components of the genetic architecture of the body mass index (BMI). We used the ITMAT-Broad-Candidate Gene Association Resource (CARe) (IBC) array comprising up to 49 320 single nucleotide polymorphisms (SNPs) across ~2100 metabolic and cardiovascular-related loci to genotype up to 108 912 individuals of European ancestry (EA), African-Americans, Hispanics and East Asians, from 46 studies, to provide additional insight into SNPs underpinning BMI. We used a five-phase study design: Phase I focused on meta-analysis of EA studies providing individual level genotype data; Phase II performed a replication of cohorts providing summary level EA data; Phase III meta-analyzed results from the first two phases; associated SNPs from Phase III were used for replication in Phase IV; finally in Phase V, a multi-ethnic meta-analysis of all samples from four ethnicities was performed. At an array-wide significance (P < 2.40E-06), we identify novel BMI associations in loci translocase of outer mitochondrial membrane 40 homolog (yeast) - apolipoprotein E - apolipoprotein C-I (TOMM40-APOE-APOC1) (rs2075650, P = 2.95E-10), sterol regulatory element binding transcription factor 2 (SREBF2, rs5996074, P = 9.43E-07) and neurotrophic tyrosine kinase, receptor, type 2 [NTRK2, a brain-derived neurotrophic factor (BDNF) receptor gene, rs1211166, P = 1.04E-06] in the Phase IV meta-analysis. Of 10 loci with previous evidence for BMI association represented on the IBC array, eight were replicated, with the remaining two showing nominal significance. Conditional analyses revealed two independent BMI-associated signals in BDNF and melanocortin 4 receptor (MC4R) regions. Of the 11 array-wide significant SNPs, three are associated with gene expression levels in both primary B-cells and monocytes; with rs4788099 in SH2B adaptor protein 1 (SH2B1) notably being associated with the expression of multiple genes in cis. These multi

  18. SU-E-J-261: Statistical Analysis and Chaotic Dynamics of Respiratory Signal of Patients in BodyFix

    SciTech Connect

    Michalski, D; Huq, M; Bednarz, G; Lalonde, R; Yang, Y; Heron, D

    2014-06-01

    Purpose: To quantify respiratory signal of patients in BodyFix undergoing 4DCT scan with and without immobilization cover. Methods: 20 pairs of respiratory tracks recorded with RPM system during 4DCT scan were analyzed. Descriptive statistic was applied to selected parameters of exhale-inhale decomposition. Standardized signals were used with the delay method to build orbits in embedded space. Nonlinear behavior was tested with surrogate data. Sample entropy SE, Lempel-Ziv complexity LZC and the largest Lyapunov exponents LLE were compared. Results: Statistical tests show difference between scans for inspiration time and its variability, which is bigger for scans without cover. The same is for variability of the end of exhalation and inhalation. Other parameters fail to show the difference. For both scans respiratory signals show determinism and nonlinear stationarity. Statistical test on surrogate data reveals their nonlinearity. LLEs show signals chaotic nature and its correlation with breathing period and its embedding delay time. SE, LZC and LLE measure respiratory signal complexity. Nonlinear characteristics do not differ between scans. Conclusion: Contrary to expectation cover applied to patients in BodyFix appears to have limited effect on signal parameters. Analysis based on trajectories of delay vectors shows respiratory system nonlinear character and its sensitive dependence on initial conditions. Reproducibility of respiratory signal can be evaluated with measures of signal complexity and its predictability window. Longer respiratory period is conducive for signal reproducibility as shown by these gauges. Statistical independence of the exhale and inhale times is also supported by the magnitude of LLE. The nonlinear parameters seem more appropriate to gauge respiratory signal complexity since its deterministic chaotic nature. It contrasts with measures based on harmonic analysis that are blind for nonlinear features. Dynamics of breathing, so crucial for

  19. Dynamics of a Definition: A Framework to Analyse Student Construction of the Concept of Solution to a Differential Equation

    ERIC Educational Resources Information Center

    Raychaudhuri, Debasree

    2008-01-01

    In this note we develop a framework that makes explicit the inherent dynamic structure of certain mathematical definitions by means of the four facets of context-entity-process-object. These facets and their interrelations are then used to capture and interpret specific aspects of student constructions of the concept of solution to first order…

  20. beta2-adrenergic receptor signaling and desensitization elucidated by quantitative modeling of real time cAMP dynamics.

    PubMed

    Violin, Jonathan D; DiPilato, Lisa M; Yildirim, Necmettin; Elston, Timothy C; Zhang, Jin; Lefkowitz, Robert J

    2008-02-01

    G protein-coupled receptor signaling is dynamically regulated by multiple feedback mechanisms, which rapidly attenuate signals elicited by ligand stimulation, causing desensitization. The individual contributions of these mechanisms, however, are poorly understood. Here, we use an improved fluorescent biosensor for cAMP to measure second messenger dynamics stimulated by endogenous beta(2)-adrenergic receptor (beta(2)AR) in living cells. beta(2)AR stimulation with isoproterenol results in a transient pulse of cAMP, reaching a maximal concentration of approximately 10 microm and persisting for less than 5 min. We investigated the contributions of cAMP-dependent kinase, G protein-coupled receptor kinases, and beta-arrestin to the regulation of beta(2)AR signal kinetics by using small molecule inhibitors, small interfering RNAs, and mouse embryonic fibroblasts. We found that the cAMP response is restricted in duration by two distinct mechanisms in HEK-293 cells: G protein-coupled receptor kinase (GRK6)-mediated receptor phosphorylation leading to beta-arrestin mediated receptor inactivation and cAMP-dependent kinase-mediated induction of cAMP metabolism by phosphodiesterases. A mathematical model of beta(2)AR signal kinetics, fit to these data, revealed that direct receptor inactivation by cAMP-dependent kinase is insignificant but that GRK6/beta-arrestin-mediated inactivation is rapid and profound, occurring with a half-time of 70 s. This quantitative system analysis represents an important advance toward quantifying mechanisms contributing to the physiological regulation of receptor signaling.

  1. Signal enhancement in optical projection tomography via virtual high dynamic range imaging of single exposure

    NASA Astrophysics Data System (ADS)

    Yang, Yujie; Dong, Di; Shi, Liangliang; Wang, Jun; Yang, Xin; Tian, Jie

    2015-03-01

    Optical projection tomography (OPT) is a mesoscopic scale optical imaging technique for specimens between 1mm and 10mm. OPT has been proven to be immensely useful in a wide variety of biological applications, such as developmental biology and pathology, but its shortcomings in imaging specimens containing widely differing contrast elements are obvious. The longer exposure for high intensity tissues may lead to over saturation of other areas, whereas a relatively short exposure may cause similarity with surrounding background. In this paper, we propose an approach to make a trade-off between capturing weak signals and revealing more details for OPT imaging. This approach consists of three steps. Firstly, the specimens are merely scanned in 360 degrees above a normal exposure but non-overexposure to acquire the projection data. This reduces the photo bleaching and pre-registration computation compared with multiple different exposures in conventional high dynamic range (HDR) imaging method. Secondly, three virtual channels are produced for each projection image based on the histogram distribution to simulate the low, normal and high exposure images used in the traditional HDR technology in photography. Finally, each virtual channel is normalized to the full gray scale range and three channels are recombined into one image using weighting coefficients optimized by a standard eigen-decomposition method. After applying our approach on the projection data, filtered back projection (FBP) algorithm is carried out for 3-dimentional reconstruction. The neonatal wild-type mouse paw has been scanned to verify this approach. Results demonstrated the effectiveness of the proposed approach.

  2. Dynamic analysis of MAPK signaling using a high-throughput microfluidic single-cell imaging platform.

    PubMed

    Taylor, R J; Falconnet, D; Niemistö, A; Ramsey, S A; Prinz, S; Shmulevich, I; Galitski, T; Hansen, C L

    2009-03-10

    Cells have evolved biomolecular networks that process and respond to changing chemical environments. Understanding how complex protein interactions give rise to emergent network properties requires time-resolved analysis of cellular response under a large number of genetic perturbations and chemical environments. To date, the lack of technologies for scalable cell analysis under well-controlled and time-varying conditions has made such global studies either impossible or impractical. To address this need, we have developed a high-throughput microfluidic imaging platform for single-cell studies of network response under hundreds of combined genetic perturbations and time-varying stimulant sequences. Our platform combines programmable on-chip mixing and perfusion with high-throughput image acquisition and processing to perform 256 simultaneous time-lapse live-cell imaging experiments. Nonadherent cells are captured in an array of 2,048 microfluidic cell traps to allow for the imaging of eight different genotypes over 12 h and in response to 32 unique sequences of stimulation, generating a total of 49,000 images per run. Using 12 devices, we carried out >3,000 live-cell imaging experiments to investigate the mating pheromone response in Saccharomyces cerevisiae under combined genetic perturbations and changing environmental conditions. Comprehensive analysis of 11 deletion mutants reveals both distinct thresholds for morphological switching and new dynamic phenotypes that are not observed in static conditions. For example, kss1Delta, fus3Delta, msg5Delta, and ptp2Delta mutants exhibit distinctive stimulus-frequency-dependent signaling phenotypes, implicating their role in filtering and network memory. The combination of parallel microfluidic control with high-throughput imaging provides a powerful tool for systems-level studies of single-cell decision making.

  3. Dynamic full field optical coherence tomography: subcellular metabolic contrast revealed in tissues by interferometric signals temporal analysis

    PubMed Central

    Apelian, Clement; Harms, Fabrice; Thouvenin, Olivier; Boccara, A. Claude

    2016-01-01

    We developed a new endogenous approach to reveal subcellular metabolic contrast in fresh ex vivo tissues taking advantage of the time dependence of the full field optical coherence tomography interferometric signals. This method reveals signals linked with local activity of the endogenous scattering elements which can reveal cells where other OCT-based techniques fail or need exogenous contrast agents. We benefit from the micrometric transverse resolution of full field OCT to image intracellular features. We used this time dependence to identify different dynamics at the millisecond scale on a wide range of organs in normal or pathological conditions. PMID:27446672

  4. Common language or Tower of Babel? On the evolutionary dynamics of signals and their meanings.

    PubMed Central

    van Baalen, Minus; Jansen, Vincent A A

    2003-01-01

    We investigate how the evolution of communication strategies affects signal credibility when there is common interest as well as a conflict between communicating individuals. Taking alarm calls as an example, we show that if the temptation to cheat is low, a single signal is used in the population. If the temptation increases cheaters will erode the credibility of a signal, and an honest mutant using a different signal ('a private code') will be very successful until this, in turn, is cracked by cheaters. In such a system, signal use fluctuates in time and space and hence the meaning of a given signal is not constant. When the temptation to cheat is too large, no honest communication can maintain itself in a Tower of Babel of many signals. We discuss our analysis in the light of the Green Beard mechanism for the evolution of altruism. PMID:12590773

  5. Common language or Tower of Babel? On the evolutionary dynamics of signals and their meanings.

    PubMed

    van Baalen, Minus; Jansen, Vincent A A

    2003-01-07

    We investigate how the evolution of communication strategies affects signal credibility when there is common interest as well as a conflict between communicating individuals. Taking alarm calls as an example, we show that if the temptation to cheat is low, a single signal is used in the population. If the temptation increases cheaters will erode the credibility of a signal, and an honest mutant using a different signal ('a private code') will be very successful until this, in turn, is cracked by cheaters. In such a system, signal use fluctuates in time and space and hence the meaning of a given signal is not constant. When the temptation to cheat is too large, no honest communication can maintain itself in a Tower of Babel of many signals. We discuss our analysis in the light of the Green Beard mechanism for the evolution of altruism.

  6. How Intrinsic Molecular Dynamics Control Intramolecular Communication in Signal Transducers and Activators of Transcription Factor STAT5

    PubMed Central

    Langenfeld, Florent; Guarracino, Yann; Arock, Michel; Trouvé, Alain; Tchertanov, Luba

    2015-01-01

    Signal Transducer and Activator of Transcription STAT5 is a key mediator of cell proliferation, differentiation and survival. While STAT5 activity is tightly regulated in normal cells, its constitutive activation directly contributes to oncogenesis and is associated with a broad range of hematological and solid tumor cancers. Therefore the development of compounds able to modulate pathogenic activation of this protein is a very challenging endeavor. A crucial step of drug design is the understanding of the protein conformational features and the definition of putative binding site(s) for such modulators. Currently, there is no structural data available for human STAT5 and our study is the first footprint towards the description of structure and dynamics of this protein. We investigated structural and dynamical features of the two STAT5 isoforms, STAT5a and STAT5b, taken into account their phosphorylation status. The study was based on the exploration of molecular dynamics simulations by different analytical methods. Despite the overall folding similarity of STAT5 proteins, the MD conformations display specific structural and dynamical features for each protein, indicating first, sequence-encoded structural properties and second, phosphorylation-induced effects which contribute to local and long-distance structural rearrangements interpreted as allosteric event. Further examination of the dynamical coupling between distant sites provides evidence for alternative profiles of the communication pathways inside and between the STAT5 domains. These results add a new insight to the understanding of the crucial role of intrinsic molecular dynamics in mediating intramolecular signaling in STAT5. Two pockets, localized in close proximity to the phosphotyrosine-binding site and adjacent to the channel for communication pathways across STAT5, may constitute valid targets to develop inhibitors able to modulate the function-related communication properties of this signaling

  7. Numerical insight into the seismic behavior of eight masonry towers in Northern Italy: FE pushover vs non-linear dynamic analyses

    NASA Astrophysics Data System (ADS)

    Milani, Gabriele; Valente, Marco

    2015-12-01

    This study presents some FE results regarding the behavior under horizontal loads of eight existing masonry towers located in the North-East of Italy. The towers, albeit unique for geometric and architectural features, show some affinities which justify a comparative analysis, as for instance the location and the similar masonry material. Their structural behavior under horizontal loads is therefore influenced by geometrical issues, such as slenderness, walls thickness, perforations, irregularities, presence of internal vaults, etc., all features which may be responsible for a peculiar output. The geometry of the towers is deduced from both existing available documentation and in-situ surveys. On the basis of such geometrical data, a detailed 3D realistic mesh is conceived, with a point by point characterization of each single geometric element. The FE models are analysed under seismic loads acting along geometric axes of the plan section, both under non-linear static (pushover) and non-linear dynamic excitation assumptions. A damage-plasticity material model exhibiting softening in both tension and compression, already available in the commercial code Abaqus, is used for masonry. Pushover analyses are performed with both G1 and G2 horizontal loads distribution, according to Italian code requirements, along X+/- and Y+/- directions. Non-linear dynamic analyses are performed along both X and Y directions with a real accelerogram scaled to different peak ground accelerations. Some few results are presented in this paper. It is found that the results obtained with pushover analyses reasonably well fit expensive non-linear dynamic simulations, with a slightly less conservative trend.

  8. Numerical insight into the seismic behavior of eight masonry towers in Northern Italy: FE pushover vs non-linear dynamic analyses

    SciTech Connect

    Milani, Gabriele E-mail: gabriele.milani@polimi.it; Valente, Marco

    2015-12-31

    This study presents some FE results regarding the behavior under horizontal loads of eight existing masonry towers located in the North-East of Italy. The towers, albeit unique for geometric and architectural features, show some affinities which justify a comparative analysis, as for instance the location and the similar masonry material. Their structural behavior under horizontal loads is therefore influenced by geometrical issues, such as slenderness, walls thickness, perforations, irregularities, presence of internal vaults, etc., all features which may be responsible for a peculiar output. The geometry of the towers is deduced from both existing available documentation and in-situ surveys. On the basis of such geometrical data, a detailed 3D realistic mesh is conceived, with a point by point characterization of each single geometric element. The FE models are analysed under seismic loads acting along geometric axes of the plan section, both under non-linear static (pushover) and non-linear dynamic excitation assumptions. A damage-plasticity material model exhibiting softening in both tension and compression, already available in the commercial code Abaqus, is used for masonry. Pushover analyses are performed with both G1 and G2 horizontal loads distribution, according to Italian code requirements, along X+/− and Y+/− directions. Non-linear dynamic analyses are performed along both X and Y directions with a real accelerogram scaled to different peak ground accelerations. Some few results are presented in this paper. It is found that the results obtained with pushover analyses reasonably well fit expensive non-linear dynamic simulations, with a slightly less conservative trend.

  9. Computational Fluid Dynamics (CFD) analyses in support of Space Shuttle Main Engine (SSME) heat exchanger (HX) vane cracking investigation

    NASA Astrophysics Data System (ADS)

    Garcia, Roberto; Benjamin, Theodore G.; Cornelison, J.; Fredmonski, A. J.

    1993-07-01

    Integration issues involved with installing the alternate turbopump (ATP) High Pressure Oxygen Turbopump (HPOTP) into the SSME have raised questions regarding the flow in the HPOTP turnaround duct (TAD). Steady-state Navier-Stokes CFD analyses have been performed by NASA and Pratt & Whitney (P&W) to address these questions. The analyses have consisted of two-dimensional axisymmetric calculations done at Marshall Space Flight Center and three-dimensional calculations performed at P&W. These analyses have identified flowfield differences between the baseline ATP and the Rocketdyne configurations. The results show that the baseline ATP configuration represents a more severe environment to the inner HX guide vane. This vane has limited life when tested in conjunction with the ATP but infinite life when tested with the current SSME HPOTP. The CFD results have helped interpret test results and have been used to assess proposed redesigns. This paper includes details of the axisymmetric model, its results, and its contribution towards resolving the problem.

  10. Rho GTPases at the crossroad of signaling networks in mammals: impact of Rho-GTPases on microtubule organization and dynamics.

    PubMed

    Wojnacki, José; Quassollo, Gonzalo; Marzolo, María-Paz; Cáceres, Alfredo

    2014-01-01

    Microtubule (MT) organization and dynamics downstream of external cues is crucial for maintaining cellular architecture and the generation of cell asymmetries. In interphase cells RhoA, Rac, and Cdc42, conspicuous members of the family of small Rho GTPases, have major roles in modulating MT stability, and hence polarized cell behaviors. However, MTs are not mere targets of Rho GTPases, but also serve as signaling platforms coupling MT dynamics to Rho GTPase activation in a variety of cellular conditions. In this article, we review some of the key studies describing the reciprocal relationship between small Rho-GTPases and MTs during migration and polarization.

  11. Notes on simulating two-dimensional Raman and terahertz-Raman signals with a full molecular dynamics simulation approach

    PubMed Central

    Ito, Hironobu; Jo, Ju-Yeon; Tanimura, Yoshitaka

    2015-01-01

    Recent developments in two-dimensional (2D) THz-Raman and 2D Raman spectroscopies have created the possibility for quantitatively investigating the role of many dynamic and structural aspects of the molecular system. We explain the significant points for properly simulating 2D vibrational spectroscopic studies of intermolecular modes using the full molecular dynamics approach, in particular, regarding the system size, the treatment of the thermostat, and inclusion of an Ewald summation for the induced polarizability. Moreover, using the simulation results for water employing various polarization functions, we elucidate the roles of permanent and induced optical properties in determining the 2D profiles of the signal. PMID:26798823

  12. Potential dynamics of the human striate cortex cerebrum realistic neural network under the influence of an external signal

    NASA Astrophysics Data System (ADS)

    Melnikov, Leonid A.; Novosselova, Anna V.; Blinova, Nadejda V.; Vinitsky, Sergey I.; Serov, Vladislav V.; Bakutkin, Valery V.; Camenskich, T. G.; Guileva, E. V.

    2000-03-01

    In this work the numerical investigations of a potential dynamics of a neural network as the non-linear system and dynamics of the visual nerve which connect the eye retina receptors with the striate cortex cerebrum as the answer to the through-skin excitement of the eye retina by the electrical signal were realized. The visual evoked potential is the answer and characterizes the human brain state over the structures retina state and the conduction of the visual nerve fibers. The results of these investigations were presented. Specific features of the neural network, such as the excitation and depression, we took into account too. The discussion about the model parameters, used at the time of the numerical investigation, was made. The comparative analysis of the retina potential data and the data of the external signal filing by the brain hemicerebrum visual centers was made too.

  13. Dynamic Hilbert warping, a new measure of RR-interval signals evaluated in the cognitive load estimation.

    PubMed

    Ghaderyan, Peyvand; Abbasi, Ataollah

    2017-02-01

    RR interval (RRI) signals represent the time intervals between successive heart R-waves. These signals are influenced by many cognitive and psychological processes. In this study, a new technique based on the combination of empirical mode decomposition and dynamic Hilbert warping (DHW) was proposed to inference cognitive states from measured RRI signals. Moreover, a set of entropic and statistical measures was extracted to characterize the regularity and temporal distribution in the phase spectra and amplitude envelope of the analytic signals. The discriminating capability of the proposed method was studied in 45 healthy subjects. They performed an arithmetic task with five levels of difficulty. The study indicated the importance of phase information in cognitive load estimation (CLE). The new phase characteristics were able to extract hidden information from the RRI signals. The results revealed a striking decrease in DHW value with increasing load level. The entropic measures of analytic signal also showed an increasing trend as the mental load increased. Although, phase information had an ability to discriminate between more distinct levels as well as between more similar ones, amplitude information was effective only in discriminating between more distinct levels.

  14. Microprocessor-based multichannel flutter monitor using dynamic strain gage signals

    NASA Technical Reports Server (NTRS)

    Smalley, R. R.

    1976-01-01

    Two microprocessor-based multichannel monitors for monitoring strain gage signals during aerodynamic instability (flutter) testing in production type turbojet engines were described. One system monitors strain gage signals in the time domain and gives an output indication whenever the signal amplitude of any gage exceeds a pre-set alarm or abort level for that particular gage. The second system monitors the strain gage signals in the frequency domain and therefore is able to use both the amplitude and frequency information. Thus, an alarm signal is given whenever the spectral content of the strain gage signal exceeds, at any point, its corresponding amplitude vs. frequency limit profiles. Each system design is described with details on design trade-offs, hardware, software, and operating experience.

  15. Molecular docking and dynamics simulation analyses unraveling the differential enzymatic catalysis by plant and fungal laccases with respect to lignin biosynthesis and degradation.

    PubMed

    Awasthi, Manika; Jaiswal, Nivedita; Singh, Swati; Pandey, Veda P; Dwivedi, Upendra N

    2015-09-01

    Laccase, widely distributed in bacteria, fungi, and plants, catalyzes the oxidation of wide range of compounds. With regards to one of the important physiological functions, plant laccases are considered to catalyze lignin biosynthesis while fungal laccases are considered for lignin degradation. The present study was undertaken to explain this dual function of laccases using in-silico molecular docking and dynamics simulation approaches. Modeling and superimposition analyses of one each representative of plant and fungal laccases, namely, Populus trichocarpa and Trametes versicolor, respectively, revealed low level of similarity in the folding of two laccases at 3D levels. Docking analyses revealed significantly higher binding efficiency for lignin model compounds, in proportion to their size, for fungal laccase as compared to that of plant laccase. Residues interacting with the model compounds at the respective enzyme active sites were found to be in conformity with their role in lignin biosynthesis and degradation. Molecular dynamics simulation analyses for the stability of docked complexes of plant and fungal laccases with lignin model compounds revealed that tetrameric lignin model compound remains attached to the active site of fungal laccase throughout the simulation period, while it protrudes outwards from the active site of plant laccase. Stability of these complexes was further analyzed on the basis of binding energy which revealed significantly higher stability of fungal laccase with tetrameric compound than that of plant. The overall data suggested a situation favorable for the degradation of lignin polymer by fungal laccase while its synthesis by plant laccase.

  16. Exploring Molecular Mechanisms of Paradoxical Activation in the BRAF Kinase Dimers: Atomistic Simulations of Conformational Dynamics and Modeling of Allosteric Communication Networks and Signaling Pathways

    PubMed Central

    Tse, Amanda; Verkhivker, Gennady M.

    2016-01-01

    The recent studies have revealed that most BRAF inhibitors can paradoxically induce kinase activation by promoting dimerization and enzyme transactivation. Despite rapidly growing number of structural and functional studies about the BRAF dimer complexes, the molecular basis of paradoxical activation phenomenon is poorly understood and remains largely hypothetical. In this work, we have explored the relationships between inhibitor binding, protein dynamics and allosteric signaling in the BRAF dimers using a network-centric approach. Using this theoretical framework, we have combined molecular dynamics simulations with coevolutionary analysis and modeling of the residue interaction networks to determine molecular determinants of paradoxical activation. We have investigated functional effects produced by paradox inducer inhibitors PLX4720, Dabrafenib, Vemurafenib and a paradox breaker inhibitor PLX7904. Functional dynamics and binding free energy analyses of the BRAF dimer complexes have suggested that negative cooperativity effect and dimer-promoting potential of the inhibitors could be important drivers of paradoxical activation. We have introduced a protein structure network model in which coevolutionary residue dependencies and dynamic maps of residue correlations are integrated in the construction and analysis of the residue interaction networks. The results have shown that coevolutionary residues in the BRAF structures could assemble into independent structural modules and form a global interaction network that may promote dimerization. We have also found that BRAF inhibitors could modulate centrality and communication propensities of global mediating centers in the residue interaction networks. By simulating allosteric communication pathways in the BRAF structures, we have determined that paradox inducer and breaker inhibitors may activate specific signaling routes that correlate with the extent of paradoxical activation. While paradox inducer inhibitors may

  17. Analysing perturbations and nonstationarity in data series using techniques motiviated by the theory of chaotic nonlinear dynamical systems

    SciTech Connect

    Downing, D.J.; Fedorov, V.; Lawkins, W.F.; Morris, M.D.; Ostrouchov, G.

    1996-05-01

    Large data series with more than several million multivariate observations, representing tens of megabytes or even gigabytes of data, are difficult or impossible to analyze with traditional software. The shear amount of data quickly overwhelms both the available computing resources and the ability of the investigator to confidently identify meaningful patterns and trends which may be present. The purpose of this research is to give meaningful definition to `large data set analysis` and to describe and illustrate a technique for identifying unusual events in large data series. The technique presented here is based on the theory of nonlinear dynamical systems.

  18. Ubx dynamically regulates Dpp signaling by repressing Dad expression during copper cell regeneration in the adult Drosophila midgut.

    PubMed

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-11-15

    The gastrointestinal (GI) tract of metazoans is lined by a series of regionally distinct epithelia. To maintain structure and function of the GI tract, regionally diversified differentiation of somatic stem cell (SC) lineages is critical. The adult Drosophila midgut provides an accessible model to study SC regulation and specification in a regionally defined manner. SCs of the posterior midgut (PM) have been studied extensively, but the control of SCs in the middle midgut (MM) is less well understood. The MM contains a stomach-like copper cell region (CCR) that is regenerated by gastric stem cells (GSSCs) and contains acid-secreting copper cells (CCs). Bmp-like Decapentaplegic (Dpp) signaling determines the identity of GSSCs, and is required for CC regeneration, yet the precise control of Dpp signaling activity in this lineage remains to be fully established. Here, we show that Dad, a negative feedback regulator of Dpp signaling, is dynamically regulated in the GSSC lineage to allow CC differentiation. Dad is highly expressed in GSSCs and their first daughter cells, the gastroblasts (GBs), but has to be repressed in differentiating CCs to allow Dpp-mediated differentiation into CCs. We find that the Hox gene ultrabithorax (Ubx) is required for this regulation. Loss of Ubx prevents Dad repression in the CCR, resulting in defective CC regeneration. Our study highlights the need for dynamic control of Dpp signaling activity in the differentiation of the GSSC lineage and identifies Ubx as a critical regulator of this process.

  19. Three-dimensional dynamic analyses of track-embankment-ground system subjected to high speed train loads.

    PubMed

    Fu, Qiang; Zheng, Changjie

    2014-01-01

    A three-dimensional finite element model was developed to investigate dynamic response of track-embankment-ground system subjected to moving loads caused by high speed trains. The track-embankment-ground systems such as the sleepers, the ballast, the embankment, and the ground are represented by 8-noded solid elements. The infinite elements are used to represent the infinite boundary condition to absorb vibration waves induced by the passing of train load at the boundary. The loads were applied on the rails directly to simulate the real moving loads of trains. The effects of train speed on dynamic response of the system are considered. The effect of material parameters, especially the modulus changes of ballast and embankment, is taken into account to demonstrate the effectiveness of strengthening the ballast, embankment, and ground for mitigating system vibration in detail. The numerical results show that the model is reliable for predicting the amplitude of vibrations produced in the track-embankment-ground system by high-speed trains. Stiffening of fill under the embankment can reduce the vibration level, on the other hand, it can be realized by installing a concrete slab under the embankment. The influence of axle load on the vibration of the system is obviously lower than that of train speed.

  20. Ancient DNA analyses exclude humans as the driving force behind late Pleistocene musk ox (Ovibos moschatus) population dynamics.

    PubMed

    Campos, Paula F; Willerslev, Eske; Sher, Andrei; Orlando, Ludovic; Axelsson, Erik; Tikhonov, Alexei; Aaris-Sørensen, Kim; Greenwood, Alex D; Kahlke, Ralf-Dietrich; Kosintsev, Pavel; Krakhmalnaya, Tatiana; Kuznetsova, Tatyana; Lemey, Philippe; MacPhee, Ross; Norris, Christopher A; Shepherd, Kieran; Suchard, Marc A; Zazula, Grant D; Shapiro, Beth; Gilbert, M Thomas P

    2010-03-23

    The causes of the late Pleistocene megafaunal extinctions are poorly understood. Different lines of evidence point to climate change, the arrival of humans, or a combination of these events as the trigger. Although many species went extinct, others, such as caribou and bison, survived to the present. The musk ox has an intermediate story: relatively abundant during the Pleistocene, it is now restricted to Greenland and the Arctic Archipelago. In this study, we use ancient DNA sequences, temporally unbiased summary statistics, and Bayesian analytical techniques to infer musk ox population dynamics throughout the late Pleistocene and Holocene. Our results reveal that musk ox genetic diversity was much higher during the Pleistocene than at present, and has undergone several expansions and contractions over the past 60,000 years. Northeast Siberia was of key importance, as it was the geographic origin of all samples studied and held a large diverse population until local extinction at approximately 45,000 radiocarbon years before present ((14)C YBP). Subsequently, musk ox genetic diversity reincreased at ca. 30,000 (14)C YBP, recontracted at ca. 18,000 (14)C YBP, and finally recovered in the middle Holocene. The arrival of humans into relevant areas of the musk ox range did not affect their mitochondrial diversity, and both musk ox and humans expanded into Greenland concomitantly. Thus, their population dynamics are better explained by a nonanthropogenic cause (for example, environmental change), a hypothesis supported by historic observations on the sensitivity of the species to both climatic warming and fluctuations.

  1. Three-Dimensional Dynamic Analyses of Track-Embankment-Ground System Subjected to High Speed Train Loads

    PubMed Central

    2014-01-01

    A three-dimensional finite element model was developed to investigate dynamic response of track-embankment-ground system subjected to moving loads caused by high speed trains. The track-embankment-ground systems such as the sleepers, the ballast, the embankment, and the ground are represented by 8-noded solid elements. The infinite elements are used to represent the infinite boundary condition to absorb vibration waves induced by the passing of train load at the boundary. The loads were applied on the rails directly to simulate the real moving loads of trains. The effects of train speed on dynamic response of the system are considered. The effect of material parameters, especially the modulus changes of ballast and embankment, is taken into account to demonstrate the effectiveness of strengthening the ballast, embankment, and ground for mitigating system vibration in detail. The numerical results show that the model is reliable for predicting the amplitude of vibrations produced in the track-embankment-ground system by high-speed trains. Stiffening of fill under the embankment can reduce the vibration level, on the other hand, it can be realized by installing a concrete slab under the embankment. The influence of axle load on the vibration of the system is obviously lower than that of train speed. PMID:24723838

  2. A new inertial aid method for high dynamic Compass signal tracking based on a nonlinear tracking differentiator.

    PubMed

    Guo, Yao; Wu, Wenqi; Tang, Kanghua

    2012-01-01

    In Compass/INS integrated navigation systems, feedback inertial navigation solutions to baseband tracking loops may eliminate receiver dynamic effects, and effectively improve the tracking accuracy and sensitivity. In the conventional inertially-aided tracking loop, the satellite-receiver line-of-sight velocity is used directly to adjust local carrier frequency. However, if the inertial solution drifts, the phase tracking error will be enlarged. By using Kalman filter based carrier phase tracking loop, this paper introduces a new inertial aid method, in which the line-of-sight jerk obtained from inertial acceleration by a nonlinear tracking differentiator is used to adjust relevant parameters of the Kalman filter's process noise matrix. Validation is achieved through high dynamic Compass B3 signal with line-of-sight jerk of 10 g/s collected by a GNSS simulator. Experimental results indicate that the new inertial aid method proposed in this paper is free of the impact of the receiver dynamic and inertial errors. Therefore, when the integrated navigation system is starting or re-tracking after losing lock, the inertial error is absent from the navigation solution correction that induces large drift, and the new aid method proposed in this paper can track highly dynamic signals.

  3. Dopamine Dynamics and Signaling in Drosophila: An Overview of Genes, Drugs and Behavioral Paradigms

    PubMed Central

    Yamamoto, Shinya; Seto, Elaine S.

    2014-01-01

    Changes in dopamine (DA) signaling have been implicated in a number of human neurologic and psychiatric disorders. Similarly, defects in DA signaling in the fruit fly, Drosophila melanogaster, have also been associated with several behavioral defects. As most genes involved in DA synthesis, transport, secretion, and signaling are conserved between species, Drosophila is a powerful genetic model organism to study the regulation of DA signaling in vivo. In this review, we will provide an overview of the genes and drugs that regulate DA biology in Drosophila. Furthermore, we will discuss the behavioral paradigms that are regulated by DA signaling in flies. By analyzing the genes and neuronal circuits that govern such behaviors using sophisticated genetic, pharmacologic, electrophysiologic, and imaging approaches in Drosophila, we will likely gain a better understanding about how this neuromodulator regulates motor tasks and cognition in humans. PMID:24770636

  4. Pair dynamics and the intermolecular nuclear Overhauser effect (NOE) in liquids analysed by simulation and model theories: Application to an ionic liquid

    SciTech Connect

    Gabl, Sonja; Schröder, Christian; Braun, Daniel; Steinhauser, Othmar; Weingärtner, Hermann

    2014-05-14

    Combining simulation and model theories, this paper analyses the impact of pair dynamics on the intermolecular nuclear Overhauser effect (NOE) in liquids. For the first time, we give a distance resolved NOE. When applied to the ionic liquid 1-ethyl-3-methyl-imidazolium tetrafluoroborate the NOE turns out to be of long-range nature. This behaviour translates to the experimentally measured cross- and longitudinal relaxation rates. We were able to calculate the heteronuclear NOE from simulation data, despite the high computational effort. Model theories are computationally less demanding and cover the complete frequency range of the respective spectral density function, they are usually based on a very simple pair distribution function and the solution of the diffusion equation. In order to model the simulated data sufficiently, these simplifications in structure and dynamics have to be generalised considerably.

  5. Dynamic Associations of Change in Physical Activity and Change in Cognitive Function: Coordinated Analyses of Four Longitudinal Studies

    PubMed Central

    Lindwall, Magnus; Cimino, Cynthia R.; Gibbons, Laura E.; Mitchell, Meghan B.; Benitez, Andreana; Brown, Cassandra L.; Kennison, Robert F.; Shirk, Steven D.; Atri, Alireza; Robitaille, Annie; MacDonald, Stuart W. S.; Zelinski, Elizabeth M.; Willis, Sherry L.; Schaie, K. Warner; Johansson, Boo; Praetorius, Marcus; Dixon, Roger A.; Mungas, Dan M.; Hofer, Scott M.; Piccinin, Andrea M.

    2012-01-01

    The present study used a coordinated analyses approach to examine the association of physical activity and cognitive change in four longitudinal studies. A series of multilevel growth models with physical activity included both as a fixed (between-person) and time-varying (within-person) predictor of four domains of cognitive function (reasoning, memory, fluency, and semantic knowledge) was used. Baseline physical activity predicted fluency, reasoning and memory in two studies. However, there was a consistent pattern of positive relationships between time-specific changes in physical activity and time-specific changes in cognition, controlling for expected linear trajectories over time, across all four studies. This pattern was most evident for the domains of reasoning and fluency. PMID:23029615

  6. SRM Internal Flow Tests and Computational Fluid Dynamic Analysis. Volume 3; Titan, ASRM, and Subscale Motor Analyses

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A computational fluid dynamics (CFD) analysis has been performed on the aft slot region of the Titan 4 Solid Rocket Motor Upgrade (SRMU). This analysis was performed in conjunction with MSFC structural modeling of the propellant grain to determine if the flow field induced stresses would adversely alter the propellant geometry to the extent of causing motor failure. The results of the coupled CFD/stress analysis have shown that there is a continual increase of flow field resistance at the aft slot due to the aft segment propellant grain being progressively moved radially toward the centerline of the motor port. This 'bootstrapping' effect between grain radial movement and internal flow resistance is conducive to causing a rapid motor failure.

  7. A Unifying Framework for Self-consistent Gravitational Lensing and Stellar Dynamics Analyses of Early-Type Galaxies

    NASA Astrophysics Data System (ADS)

    Barnabè, Matteo; Koopmans, Léon V. E.

    2007-09-01

    Gravitational lensing and stellar dynamics are two independent methods, based solely on gravity, to study the mass distributions of galaxies. Both methods suffer from degeneracies, however, that are difficult to break. In this paper we present a new framework that self-consistently unifies gravitational lensing and stellar dynamics, breaking some classical degeneracies that have limited their individual usage, particularly in the study of high-redshift galaxies. For any given galaxy potential, the mapping of both the unknown lensed source brightness distribution and the stellar phase-space distribution function onto the photometric and kinematic observables can be cast as a single set of coupled linear equations, which are solved by maximizing the likelihood penalty function. The Bayesian evidence penalty function subsequently allows one to find the best potential-model parameters and to quantitatively rank potential-model families or other model assumptions (e.g., PSF). We have implemented a fast algorithm that solves for the maximum-likelihood pixelized lensed source brightness distribution and the two-integral stellar phase-space distribution function f(E,Lz), assuming axisymmetric potentials. To make the method practical, we have devised a new Monte Carlo approach to Schwarzschild's orbital superposition method, based on the superposition of two-integral (E and Lz) toroidal components, to find the maximum-likelihood two-integral distribution function in a matter of seconds in any axisymmetric potential. The nonlinear parameters of the potential are subsequently found through a hybrid MCMC and Simplex optimization of the evidence. Illustrated by the power-law potential models of Evans, we show that the inclusion of stellar kinematic constraints allows the correct linear and nonlinear model parameters to be recovered, including the potential strength, oblateness, and inclination, which, in the case of gravitational-lensing constraints only, would otherwise be

  8. Microbial contributions to C and N dynamics in decaying litter elucidated by amino acid and amino sugar analyses

    NASA Astrophysics Data System (ADS)

    Hobara, S.; Osono, T.; Noro, K.; Hirota, M.; Benner, R. H.

    2011-12-01

    There is still much to be revealed about carbon (C) and nitrogen (N) dynamics in terrestrial soil systems. The objectives of this study were to identify molecular changes in composition during plant litter decomposition and gain insights about microbial contributions to C and N dynamics in decaying litter. Litter bag experiments with three plant species, Miscanthus sinensis, Pinus densiflora and Quercus crispula, were conducted for three years, and the concentrations of C, N, amino acids and amino sugars were determined at various times during the experiments. Mass loss (AFDW) ranged from 66-90% for the plant tissues. The weight %C remained fairly constant, whereas the weight %N increased throughout the study indicating N immobilization was occurring. The percentages of C as amino acids and amino sugars also increased throughout the study suggesting these biomolecules were largely of microbial origin. The increasing yields of amino acids and amino sugars were inversely related to overall C loss from the litter material. As microorganisms degraded the plant litter they left behind molecular signatures that were useful predictors of the extent of overall degradation. The C/N ratio of litter decreased throughout the study and was inversely related to galactosamine yields. The glucosamine/galactosamine (GlcN/GalN) ratio gradually declined to values near 2 by the end of the study. Galactoasamine is more abundant in bacteria than fungi, and the declining GlcN/GalN ratio suggest the relative contributions of bacterial to litter C and N increased relative to contributions from fungi. A cluster analysis of 0- and 36-month litters based on amino acid and amino sugar composition showed that 0-month litters of three plant species were separated from 36-month litters, suggesting common diagenetic pathways during decomposition irrespective of plant species. The microbial decomposers contribute to N immobilization and their contributions to the C and N content of litter increases

  9. Combined NMR and GC-MS analyses revealed dynamic metabolic changes associated with the carrageenan-induced rat pleurisy.

    PubMed

    Li, Huihui; An, Yanpeng; Zhang, Lulu; Lei, Hehua; Zhang, Limin; Wang, Yulan; Tang, Huiru

    2013-12-06

    Inflammation is closely associated with pathogenesis of various metabolic disorders, cardiovascular diseases, and cancers. To understand the systems responses to localized inflammation, we analyzed the dynamic metabolic changes in rat plasma and urine associated with the carrageenan-induced self-limiting pleurisy using NMR spectroscopy in conjunction with multivariate data analysis. Fatty acids in plasma were also analyzed using GC-FID/MS with the data from clinical chemistry and histopathology as complementary information. We found that in the acute phase of inflammation rats with pleurisy had significantly lower levels in serum albumin, fatty acids, and lipoproteins but higher globulin level and larger quantity of pleural exudate than controls. The carrageenan-induced inflammation was accompanied by significant metabolic alterations involving TCA cycle, glycolysis, biosyntheses of acute phase proteins, and metabolisms of amino acids, fatty acids, ketone bodies, and choline in acute phase. The resolution process of pleurisy was heterogeneous, and two subgroups were observed for the inflammatory rats at day-6 post treatment with different metabolic features together with the quantity of pleural exudate and weights of thymus and spleen. The metabolic differences between these subgroups were reflected in the levels of albumin and acute-phase proteins, the degree of returning to normality for multiple metabolic pathways including glycolysis, TCA cycle, gut microbiota functions, and metabolisms of lipids, choline and vitamin B3. These findings provided some essential details for the dynamic metabolic changes associated with the carrageenan-induced self-limiting inflammation and demonstrated the combined NMR and GC-FID/MS analysis as a powerful approach for understanding biochemical aspects of inflammation.

  10. MO-F-CAMPUS-J-03: Sorting 2D Dynamic MR Images Using Internal Respiratory Signal for 4D MRI

    SciTech Connect

    Wen, Z; Hui, C; Beddar, S; Stemkens, B; Tijssen, R; Berg, C van den

    2015-06-15

    Purpose: To develop a novel algorithm to extract internal respiratory signal (IRS) for sorting dynamic magnetic resonance (MR) images in order to achieve four-dimensional (4D) MR imaging. Methods: Dynamic MR images were obtained with the balanced steady state free precession by acquiring each two-dimensional sagittal slice repeatedly for more than one breathing cycle. To generate a robust IRS, we used 5 different representative internal respiratory surrogates in both the image space (body area) and the Fourier space (the first two low-frequency phase components in the anterior-posterior direction, and the first two low-frequency phase components in the superior-inferior direction). A clustering algorithm was then used to search for a group of similar individual internal signals, which was then used to formulate the final IRS. A phantom study and a volunteer study were performed to demonstrate the effectiveness of this algorithm. The IRS was compared to the signal from the respiratory bellows. Results: The IRS computed by our algorithm matched well with the bellows signal in both the phantom and the volunteer studies. On average, the normalized cross correlation between the IRS and the bellows signal was 0.97 in the phantom study and 0.87 in the volunteer study, respectively. The average difference between the end inspiration times in the IRS and bellows signal was 0.18 s in the phantom study and 0.14 s in the volunteer study, respectively. 4D images sorted based on the IRS showed minimal mismatched artifacts, and the motion of the anatomy was coherent with the respiratory phases. Conclusion: A novel algorithm was developed to generate IRS from dynamic MR images to achieve 4D MR imaging. The performance of the IRS was comparable to that of the bellows signal. It can be easily implemented into the clinic and potentially could replace the use of external respiratory surrogates. This research was partially funded by the the Center for Radiation Oncology Research from

  11. A dynamic Gli code interprets Hh signals to regulate induction, patterning, and endocrine cell specification in the zebrafish pituitary.

    PubMed

    Devine, Christine A; Sbrogna, Jennifer L; Guner, Burcu; Osgood, Marcey; Shen, Meng-Chieh; Karlstrom, Rolf O

    2009-02-01

    Hedgehog (Hh) signaling is necessary for the induction and functional patterning of the pituitary placode, however the mechanisms by which Hh signals are interpreted by placodal cells are unknown. Here we show distinct temporal requirements for Hh signaling in endocrine cell differentiation and describe a dynamic Gli transcriptional response code that interprets these Hh signals within the developing adenohypophysis. Gli1 is required for the differentiation of selected endocrine cell types and acts as the major activator of Hh-mediated pituitary induction, while Gli2a and Gli2b contribute more minor activator functions. Intriguingly, this Gli response code changes as development proceeds. Gli1 continues to be required for the activation of the Hh response anteriorly in the pars distalis. In contrast, Gli2b is required to repress Hh target gene expression posteriorly in the pars intermedia. Consistent with these changing roles, gli1, gli2a, and gli2b, but not gli3, are expressed in pituitary precursor cells at the anterior neural ridge. Later in development, gli1 expression is maintained throughout the adenohypophysis while gli2a and gli2b expression are restricted to the pars intermedia. Given the link between Hh signaling and pituitary adenomas in humans, our data suggest misregulation of Gli function may contribute to these common pituitary tumors.

  12. Distinct growth factor-induced dynamic mass redistribution (DMR) profiles for monitoring oncogenic signaling pathways in various cancer cells.

    PubMed

    Du, Yuhong; Li, Zijian; Li, Lian; Chen, Zhuo Georgia; Sun, Shi-Yong; Chen, Peifang; Shin, Dong M; Khuri, Fadlo R; Fu, Haian

    2009-01-01

    Targeting dysregulated signaling pathways in tumors has led to the development of a novel class of signal transduction inhibitors, including inhibitors of the epidermal growth factor (EGF) receptor (EGFR). To dissect oncogenic pathways, identify key pathway determinants, and evaluate the efficacy of targeted agents, it is vital to develop technologies that allow the detection of temporal signaling events under physiological conditions. Here we report the application of a label-free optical biosensor to reveal the rapid response of cancer cells to EGF, expressed as a dynamic mass redistribution (DMR) signal. In response to EGF, squamous cell carcinoma of the head and neck cells exhibited a rapid rise in DMR signal, whereas lung adenocarcinoma cells showed a biphasic DMR profile, suggesting a cell type-dependent DMR response. Pharmacological studies suggested the importance of EGFR and the phosphatidylinositol-3 kinase pathway in mediating the EGF-induced DMR response. The defined DMR signatures offer a simple yet sensitive tool for evaluating EGFR-targeted agents, as shown with gefitinib and erlotinib. The assay can also be used for cell-based high-throughput screening of EGF pathway inhibitors, as demonstrated by its robust performance in a 384-well plate format (Z' > 0.5). This technology is applicable to other oncogenic pathways for the discovery of novel therapeutic agents for the treatment of various cancers.

  13. Efficient detection and signal parameter estimation with applications to high dynamic GPS receivers

    NASA Technical Reports Server (NTRS)

    Kumar, R.

    1988-01-01

    A novel technique for simultaneously detecting data and estimating the parameters of a received carrier signal phase modulated by unknown data and experiencing very high Doppler, Doppler rate, etc. is discussed. Such a situation arises, for example, in the case of Global Positioning Systems (DPS) where the signal parameters are directly related to the position, velocity and acceleration of the GPS receiver. The proposed scheme is based upon first estimating the received signal local (data dependent) parameters over two consecutive bit periods, followed by the detection of a possible jump in these parameters. The presence of a detected jump signifies a data transition which is then removed from the received signal. This effectively demodulated signal is then processed to provide the estimates of global (data independent) parameters of the signal related to the position, velocity, etc. of the receiver. One of the key features of the proposed algorithm is the introduction of two different schemes which can provide an improvement of up to 3 dB over the conventional implementation of Kalman filter as applied to phase and frequency estimation, under low to medium signal-to-noise ratio conditions.

  14. Signal-quality consideration for dynamic connection provisioning in all-optical wavelength-routed networks

    NASA Astrophysics Data System (ADS)

    Huang, Yurong R.; Wen, Wushao; Heritage, Jonathan P.; Mukherjee, Biswanath

    2003-10-01

    We investigate new connection-provisioning algorithms to efficiently provide signal-quality-guaranteed connections in an all-optical WDM mesh network. In the all-optical network, signal degradations incurred by non-ideal transmission medium accumulate along a lightpath. When the signal degradation reaches a certain level, the connection is not usable and is blocked due to transmission impairments in the physical layer. To ensure high service quality of provisioned connections, it is essential to develop intelligent routing and wavelength assignment (RWA) algorithms which can combat the effects of impairments when setting up a connection. For this purpose, we propose two impairment-aware RWA algorithms, namely impairment-aware best-path (IABP) algorithm and impairment-aware first-fit (IAFF) algorithm. The optical signal-to-noise raito (OSNR) requirement and polarization mode dispersion (PMD) effect are used as signal-quality constraints to avoid setting up a connection with unacceptable quality due to the effects of transmission impairments. With the signal-quality consideration, as compared to algorithms that are not impairment aware in a realistic optical network, our proposed impairment-aware algorithms efficiently provide signal-quality-guaranteed connection while significantly reducing connection-blocking probability, better utilizing network resources, and having a reasonable computational requirement. Also, the effect of channel bit rate is studied in this paper.

  15. Dynamic Frequency Analyses of Lower Extremity Muscles during Sit-To-Stand Motion for the Patients with Knee Osteoarthritis

    PubMed Central

    Suzuki, Kentaro; Yagi, Masahide

    2016-01-01

    Objective Muscle activities during the sit-to-stand motion (STS) are characterized by coordinated movements between hip extensors and knee extensors. However, previous reports regarding the STS and lower extremity muscle activities have focused on some quantitative assessment, but little qualitative research. This study aimed to examine the muscle activities of the lower extremity both quantitatively and qualitatively. Methods Study participants included 13 patients with knee osteoarthritis (knee OA) and 11 age-matched asymptomatic controls. The task was STS from a chair with a height-adjustable seat. EMG activities were acquired using surface electromyogram. The root mean square signals normalized as a percentage of maximum voluntary isometric contraction values (RMS%MVC) and the mean power frequency (MPF) were calculated. Results During STS, knee OA patients had increased RMS%MVC of the vastus medialis and raised MPF of the rectus femoris before buttocks-off. Conclusion These findings suggest that STS of knee OA patients not only increased relative muscle activity of the vastus medialis, but also enlisted the rectus femoris in knee extension to improve muscle contraction force by activating more type II fibers to accomplish buttocks-off. PMID:26807578

  16. The AquaDEB project: Physiological flexibility of aquatic animals analysed with a generic dynamic energy budget model (phase II)

    NASA Astrophysics Data System (ADS)

    Alunno-Bruscia, Marianne; van der Veer, Henk W.; Kooijman, Sebastiaan A. L. M.

    2011-11-01

    This second special issue of the Journal of Sea Research on development and applications of Dynamic Energy Budget (DEB) theory concludes the European Research Project AquaDEB (2007-2011). In this introductory paper we summarise the progress made during the running time of this 5 years' project, present context for the papers in this volume and discuss future directions. The main scientific objectives in AquaDEB were (i) to study and compare the sensitivity of aquatic species (mainly molluscs and fish) to environmental variability within the context of DEB theory for metabolic organisation, and (ii) to evaluate the inter-relationships between different biological levels (individual, population, ecosystem) and temporal scales (life cycle, population dynamics, evolution). AquaDEB phase I focussed on quantifying bio-energetic processes of various aquatic species ( e.g. molluscs, fish, crustaceans, algae) and phase II on: (i) comparing of energetic and physiological strategies among species through the DEB parameter values and identifying the factors responsible for any differences in bioenergetics and physiology; (ii) considering different scenarios of environmental disruption (excess of nutrients, diffuse or massive pollution, exploitation by man, climate change) to forecast effects on growth, reproduction and survival of key species; (iii) scaling up the models for a few species from the individual level up to the level of evolutionary processes. Apart from the three special issues in the Journal of Sea Research — including the DEBIB collaboration (see vol. 65 issue 2), a theme issue on DEB theory appeared in the Philosophical Transactions of the Royal Society B (vol 365, 2010); a large number of publications were produced; the third edition of the DEB book appeared (2010); open-source software was substantially expanded (over 1000 functions); a large open-source systematic collection of ecophysiological data and DEB parameters has been set up; and a series of DEB

  17. Biochemical, Structural and Molecular Dynamics Analyses of the Potential Virulence Factor RipA from Yersinia pestis

    PubMed Central

    Torres, Rodrigo; Swift, Robert V.; Chim, Nicholas; Wheatley, Nicole; Lan, Benson; Atwood, Brian R.; Pujol, Céline; Sankaran, Banu; Bliska, James B.; Amaro, Rommie E.; Goulding, Celia W.

    2011-01-01

    Human diseases are attributed in part to the ability of pathogens to evade the eukaryotic immune systems. A subset of these pathogens has developed mechanisms to survive in human macrophages. Yersinia pestis, the causative agent of the bubonic plague, is a predominately extracellular pathogen with the ability to survive and replicate intracellularly. A previous study has shown that a novel rip (required for intracellular proliferation) operon (ripA, ripB and ripC) is essential for replication and survival of Y. pestis in postactivated macrophages, by playing a role in lowering macrophage-produced nitric oxide (NO) levels. A bioinformatics analysis indicates that the rip operon is conserved among a distally related subset of macrophage-residing pathogens, including Burkholderia and Salmonella species, and suggests that this previously uncharacterized pathway is also required for intracellular survival of these pathogens. The focus of this study is ripA, which encodes for a protein highly homologous to 4-hydroxybutyrate-CoA transferase; however, biochemical analysis suggests that RipA functions as a butyryl-CoA transferase. The 1.9 Å X-ray crystal structure reveals that RipA belongs to the class of Family I CoA transferases and exhibits a unique tetrameric state. Molecular dynamics simulations are consistent with RipA tetramer formation and suggest a possible gating mechanism for CoA binding mediated by Val227. Together, our structural characterization and molecular dynamic simulations offer insights into acyl-CoA specificity within the active site binding pocket, and support biochemical results that RipA is a butyryl-CoA transferase. We hypothesize that the end product of the rip operon is butyrate, a known anti-inflammatory, which has been shown to lower NO levels in macrophages. Thus, the results of this molecular study of Y. pestis RipA provide a structural platform for rational inhibitor design, which may lead to a greater understanding of the role of RipA in

  18. Dynamical analyses on the transitivity from JFC and Centaur regions to NEAs with Tisserand parameters from 2 to 3

    NASA Astrophysics Data System (ADS)

    Kaplan, Murat; Erece, Orhan; Aslan, Gürkan; Eker, Zeki

    2016-12-01

    We study the contribution of JFC (Jupiter family comet) and Centaur regions to the NEA (near Earth asteroid) population having Tisserand parameters for Jupiter between 2 and 3. We define a region for JFCs (aphelion distance (Q) > 4.61 au, perihelion distance (q) < 4.95 au, > 1.3 au) and we check the contributions of selected bodies (JFCs, Centaurs, Halley-type comets (HTCs), some elliptic comets, and some outer main belt asteroids) from various regions to the NEA region. Additionally, we integrated NEAs with Tisserand parameters for Jupiter (TJ) between 2 and 3 and their clones backward in time to see whether there was a strong dynamical path between those NEAs and the defined JFC region. As a result, 35.1% of the orbits from the defined JFC region turned out to be Earth-crossing orbits for forward integrations, while 66.7% of NEAs (2

  19. Dynamic modeling and analyses of simultaneous saccharification and fermentation process to produce bio-ethanol from rice straw.

    PubMed

    Ko, Jordon; Su, Wen-Jun; Chien, I-Lung; Chang, Der-Ming; Chou, Sheng-Hsin; Zhan, Rui-Yu

    2010-02-01

    The rice straw, an agricultural waste from Asians' main provision, was collected as feedstock to convert cellulose into ethanol through the enzymatic hydrolysis and followed by the fermentation process. When the two process steps are performed sequentially, it is referred to as separate hydrolysis and fermentation (SHF). The steps can also be performed simultaneously, i.e., simultaneous saccharification and fermentation (SSF). In this research, the kinetic model parameters of the cellulose saccharification process step using the rice straw as feedstock is obtained from real experimental data of cellulase hydrolysis. Furthermore, this model can be combined with a fermentation model at high glucose and ethanol concentrations to form a SSF model. The fermentation model is based on cybernetic approach from a paper in the literature with an extension of including both the glucose and ethanol inhibition terms to approach more to the actual plants. Dynamic effects of the operating variables in the enzymatic hydrolysis and the fermentation models will be analyzed. The operation of the SSF process will be compared to the SHF process. It is shown that the SSF process is better in reducing the processing time when the product (ethanol) concentration is high. The means to improve the productivity of the overall SSF process, by properly using aeration during the batch operation will also be discussed.

  20. History, Mechanisms and Clinical Value of Fibrillation Analyses in Muscle Denervation and Reinnervation by Single Fiber Electromyography and Dynamic Echomyography

    PubMed Central

    Pond, Amber; Zanato, Riccardo; Martino, Leonora; Stramare, Roberto; Vindigni, Vincenzo; Zampieri, Sandra; Hofer, Christian; Kern, Helmut; Masiero, Stefano; Piccione, Francesco

    2014-01-01

    This work reviews history, current clinical relevance and future of fibrillation, a functional marker of skeletal muscle denervated fibers. Fibrillations, i.e., spontaneous contraction, in denervated muscle were first described during the nineteenth century. It is known that alterations in membrane potential are responsible for the phenomenon and that they are related to changes in electrophysiological factors, cellular metabolism, cell turnover and gene expression. They are known to inhibit muscle atrophy to some degree and are used to diagnose neural injury and reinnervation that are occurring in patients. Electromyography (EMG) is useful in determining progress, prognosis and efficacy of therapeutic interventions and their eventual change. For patients with peripheral nerve injury, and thus without the option of volitional contractions, electrical muscle stimulation may be helpful in preserving the contractility and extensibility of denervated muscle tissue and in retarding/counteracting muscle atrophy. It is obvious from the paucity of recent literature that research in this area has declined over the years. This is likely a consequence of the decrease in funding available for research and the fact that the fibrillations do not appear to cause serious health issues. Nonetheless, further exploration of them as diagnostic tools in long-term denervation is merited, in particular if Single Fiber EMG (SFEMG) is combined with Dynamic Echomyography (DyEM), an Ultra Sound muscle approach we recently designed and developed to explore denervated and reinnervating muscles. PMID:26913128

  1. Computational fluid dynamics-based hydraulic and hemolytic analyses of a novel left ventricular assist blood pump.

    PubMed

    Yang, Xiao-Chen; Zhang, Yan; Gui, Xing-Min; Hu, Sheng-Shou

    2011-10-01

    The advent of various technologies has allowed mechanical blood pumps to become more reliable and versatile in recent decades. In our study group, a novel structure of axial flow blood pump was developed for assisting the left ventricle. The design point of the left ventricular assist blood pump 25 (LAP-25) was chosen at 4 Lpm with 100 mm Hg according to our clinical practice. Computational fluid dynamics was used to design and analyze the performance of the LAP-25. In order to obtain a required hydraulic performance and a satisfactory hemolytic property in the LAP-25 of a smaller size, a novel structure was developed including an integrated shroud impeller, a streamlined impeller hub, and main impeller blades with splitter blades; furthermore, tandem cascades were introduced in designing the diffuser. The results of numerical simulation show the LAP-25 can generate flow rates of 3-5 Lpm at rotational speeds of 8500-10,500 rpm, producing pressure rises of 27.5-148.3 mm Hg with hydraulic efficiency points ranging from 13.4 to 27.5%. Moreover, the fluid field and the hemolytic property of the LAP-25 were estimated, and the mean hemolysis index of the pump was 0.0895% with Heuser's estimated model. In conclusion, the design of the LAP-25 shows an acceptable result.

  2. Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction.

    PubMed Central

    Nicholson, S E; Willson, T A; Farley, A; Starr, R; Zhang, J G; Baca, M; Alexander, W S; Metcalf, D; Hilton, D J; Nicola, N A

    1999-01-01

    SOCS-1 (suppressor of cytokine signaling-1) is a representative of a family of negative regulators of cytokine signaling (SOCS-1 to SOCS-7 and CIS) characterized by a highly conserved C-terminal SOCS box preceded by an SH2 domain. This study comprehensively examined the ability of several SOCS family members to negatively regulate the gp130 signaling pathway. SOCS-1 and SOCS-3 inhibited both interleukin-6 (IL-6)- and leukemia inhibitory factor (LIF)-induced macrophage differentiation of murine monocytic leukemic M1 cells and LIF induction of a Stat3-responsive reporter construct in 293T fibroblasts. Deletion of amino acids 51-78 in the N-terminal region of SOCS-1 prevented inhibition of LIF signaling. The SOCS-1 and SOCS-3 N-terminal regions were functionally interchangeable, but this did not extend to other SOCS family members. Mutation of SH2 domains abrogated the ability of both SOCS-1 and SOCS-3 to inhibit LIF signal transduction. Unlike SOCS-1, SOCS-3 was unable to inhibit JAK kinase activity in vitro, suggesting that SOCS-1 and SOCS-3 act on the JAK-STAT pathway in different ways. Thus, although inhibition of signaling by SOCS-1 and SOCS-3 requires both the SH2 and N-terminal domains, their mechanisms of action appear to be biochemically different. PMID:9889194

  3. Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: A perspective

    PubMed Central

    Pullikuth, Ashok K.; Catling, Andrew D.

    2008-01-01

    Cell migration is critical for many physiological processes and is often misregulated in developmental disorders and pathological conditions including cancer and neurodegeneration. MAPK signaling and the Rho family of proteins are known regulators of cell migration that exert their influence on cellular cytoskeleton during cell adhesion and migration. Here we review data supporting the view that localized ERK signaling mediated through recently identified scaffold proteins may regulate cell migration. PMID:17553668

  4. Non-linear dynamic analyses of 3D masonry structures by means of a homogenized rigid body and spring model (HRBSM)

    NASA Astrophysics Data System (ADS)

    Bertolesi, Elisa; Milani, Gabriele; Casolo, Siro

    2016-12-01

    A simple homogenized rigid body and spring model (HRBSM) is presented and applied for the non-linear dynamic analysis of 3D masonry structures. The approach, previously developed by the authors for the modeling of in-plane loaded walls is herein extended to real 3D buildings subjected to in- and out-of-plane deformation modes. The elementary cell is discretized by means of three-noded plane stress elements and non-linear interfaces. At a structural level, the non-linear analyses are performed replacing the homogenized orthotropic continuum with a rigid element and non-linear spring assemblage (RBSM) by means of which both in and out of plane mechanisms are allowed. All the simulations here presented are performed using the commercial software Abaqus. In order to validate the proposed model for the analyses of full scale structures subjected to seismic actions, two different examples are critically discussed, namely a church façade and an in-scale masonry building, both subjected to dynamic excitation. The results obtained are compared with experimental or numerical results available in literature.

  5. Scratching the surface: signaling and routing dynamics of the CSF3 receptor.

    PubMed

    Palande, Karishma; Meenhuis, Annemarie; Jevdjovic, Tanja; Touw, Ivo P

    2013-01-01

    Following activation by their cognate ligands, cytokine receptors undergo intracellular routing towards lysosomes where they are degraded. Cytokine receptor signaling does not terminate at the plasma membrane, but continues throughout the endocytotic pathway. The modes of internalization and intracellular trafficking of specific receptors, the level of recycling towards the plasma membrane, the type of protein modifications (phosphorylation, ubiquitination) and the enzymes involved in these processes are remarkably diverse. This heterogeneity may contribute to the fine-tuning of signal amplitudes and duration from different receptors. The colony-stimulating factor 3 receptor (CSF3R) is unique for its balanced signaling output, first leading to proliferation of myeloid progenitors, followed by a cell cycle arrest and granulocytic differentiation. The mechanisms associated with CSF3R signal modulation, involving receptor lysine ubiquitination and redox-controlled phosphatase activities, are to a large extent confined to the signaling endosome. Interactions between signaling endosomes and the endoplasmic reticulum play a key role in this process. Here, we review the mechanisms of intracellular routing of CSF3R, their consequences for myeloid blood cell development and their implications for myeloid diseases.

  6. Characterization of Dynamic Behaviour of MCF7 and MCF10A Cells in Ultrasonic Field Using Modal and Harmonic Analyses

    PubMed Central

    Bade, Dennis; Meditz, Katharina; Witt, Reiner; Bicker, Uwe; Bludszuweit-Philipp, Catrin; Maier, Patrick

    2015-01-01

    Treatment options specifically targeting tumour cells are urgently needed in order to reduce the side effects accompanied by chemo- or radiotherapy. Differences in subcellular structure between tumour and normal cells determine their specific elasticity. These structural differences can be utilised by low-frequency ultrasound in order to specifically induce cytotoxicity of tumour cells. For further evaluation, we combined in silico FEM (finite element method) analyses and in vitro assays to bolster the significance of low-frequency ultrasound for tumour treatment. FEM simulations were able to calculate the first resonance frequency of MCF7 breast tumour cells at 21 kHz in contrast to 34 kHz for the MCF10A normal breast cells, which was due to the higher elasticity and larger size of MCF7 cells. For experimental validation of the in silico-determined resonance frequencies, equipment for ultrasonic irradiation with distinct frequencies was constructed. Differences for both cell lines in their response to low-frequent ultrasonic treatment were corroborated in 2D and in 3D cell culture assays. Treatment with ~ 24.5 kHz induced the death of MCF7 cells and MDA-MB-231 metastases cells possessing a similar elasticity; frequencies of > 29 kHz resulted in cytotoxicity of MCF10A. Fractionated treatments by ultrasonic irradiation of suspension myeloid HL60 cells resulted in a significant decrease of viable cells, mostly significant after threefold irradiation in intervals of 3 h. Most importantly in regard to a clinical application, combined ultrasonic treatment and chemotherapy with paclitaxel showed a significantly increased killing of MCF7 cells compared to both monotherapies. In summary, we were able to determine for the first time for different tumour cell lines a specific frequency of low-intensity ultrasound for induction of cell ablation. The cytotoxic effect of ultrasonic irradiation could be increased by either fractionated treatment or in combination with

  7. Diagnostic study of coupled solar wind-magnetosphere-ionosphere dynamics in D-region ionosphere via VLF signal propagation characteristic

    NASA Astrophysics Data System (ADS)

    Nwankwo, Victor U. J.; Chakrabarti, Sandip Kumar

    2016-07-01

    Geomagnetic disturbances and storms are known to produce significant global disturbances in the ionosphere, including the middle atmosphere and troposphere. There is little understanding about the mechanism and dynamics that drive these processes in lower ionosphere. The ionosphere is also thought to be sensitive to seismic events, and it is believed that it exhibits precursory characteristics as reported in studies via characteristic anomalies in VLF signal. However, distinguishing or separating seismically induced ionospheric fluctuations from those of other origins (e.g., Solar activity, planetary and tidal waves, stratospheric warming etc.) remain vital to robust conclusion, and challenging too. The unique propagation characteristic of VLF radio signal makes it an ideal tool for the study and diagnosis of variability of D-region ionosphere. In this work, we present the analysis of solar wind-magnetosphere-ionosphere coupling dynamics in D-region ionosphere using VLF signal characteristics, and performed an investigation of previously reported 'ionospheric precursors' to understand the true origins of measured anomalies.

  8. Use of restrained molecular dynamics to predict the conformations of phosphorylated receiver domains in two‐component signaling systems

    PubMed Central

    Foster, Clay A.

    2016-01-01

    ABSTRACT Two‐component signaling (TCS) is the primary means by which bacteria, as well as certain plants and fungi, respond to external stimuli. Signal transduction involves stimulus‐dependent autophosphorylation of a sensor histidine kinase and phosphoryl transfer to the receiver domain of a downstream response regulator. Phosphorylation acts as an allosteric switch, inducing structural and functional changes in the pathway's components. Due to their transient nature, phosphorylated receiver domains are challenging to characterize structurally. In this work, we provide a methodology for simulating receiver domain phosphorylation to predict conformations that are nearly identical to experimental structures. Using restrained molecular dynamics, phosphorylated conformations of receiver domains can be reliably sampled on nanosecond timescales. These simulations also provide data on conformational dynamics that can be used to identify regions of functional significance related to phosphorylation. We first validated this approach on several well‐characterized receiver domains and then used it to compare the upstream and downstream components of the fungal Sln1 phosphorelay. Our results demonstrate that this technique provides structural insight, obtained in the absence of crystallographic or NMR information, regarding phosphorylation‐induced conformational changes in receiver domains that regulate the output of their associated signaling pathway. To our knowledge, this is the first time such a protocol has been described that can be broadly applied to TCS proteins for predictive purposes. Proteins 2016; 85:155–176. © 2016 Wiley Periodicals, Inc. PMID:27802580

  9. Analysing the Effect of Mutation on Protein Function and Discovering Potential Inhibitors of CDK4: Molecular Modelling and Dynamics Studies

    PubMed Central

    N, Nagasundaram; Zhu, Hailong; Liu, Jiming; V, Karthick; C, George Priya Doss; Chakraborty, Chiranjib; Chen, Luonan

    2015-01-01

    The cyclin-dependent kinase 4 (CDK4)-cyclin D1 complex plays a crucial role in the transition from the G1 phase to S phase of the cell cycle. Among the CDKs, CDK4 is one of the genes most frequently affected by somatic genetic variations that are associated with various forms of cancer. Thus, because the abnormal function of the CDK4-cyclin D1 protein complex might play a vital role in causing cancer, CDK4 can be considered a genetically validated therapeutic target. In this study, we used a systematic, integrated computational approach to identify deleterious nsSNPs and predict their effects on protein-protein (CDK4-cyclin D1) and protein-ligand (CDK4-flavopiridol) interactions. This analysis resulted in the identification of possible inhibitors of mutant CDK4 proteins that bind the conformations induced by deleterious nsSNPs. Using computational prediction methods, we identified five nsSNPs as highly deleterious: R24C, Y180H, A205T, R210P, and R246C. From molecular docking and molecular dynamic studies, we observed that these deleterious nsSNPs affected CDK4-cyclin D1 and CDK4-flavopiridol interactions. Furthermore, in a virtual screening approach, the drug 5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDROXYPHENYL) _4H_CHROMEN_ 4_ONE displayed good binding affinity for proteins with the mutations R24C or R246C, the drug diosmin displayed good binding affinity for the protein with the mutation Y180H, and the drug rutin displayed good binding affinity for proteins with the mutations A205T and R210P. Overall, this computational investigation of the CDK4 gene highlights the link between genetic variation and biological phenomena in human cancer and aids in the discovery of molecularly targeted therapies for personalized treatment. PMID:26252490

  10. Analysing the Effect of Mutation on Protein Function and Discovering Potential Inhibitors of CDK4: Molecular Modelling and Dynamics Studies.

    PubMed

    N, Nagasundaram; Zhu, Hailong; Liu, Jiming; V, Karthick; C, George Priya Doss; Chakraborty, Chiranjib; Chen, Luonan

    2015-01-01

    The cyclin-dependent kinase 4 (CDK4)-cyclin D1 complex plays a crucial role in the transition from the G1 phase to S phase of the cell cycle. Among the CDKs, CDK4 is one of the genes most frequently affected by somatic genetic variations that are associated with various forms of cancer. Thus, because the abnormal function of the CDK4-cyclin D1 protein complex might play a vital role in causing cancer, CDK4 can be considered a genetically validated therapeutic target. In this study, we used a systematic, integrated computational approach to identify deleterious nsSNPs and predict their effects on protein-protein (CDK4-cyclin D1) and protein-ligand (CDK4-flavopiridol) interactions. This analysis resulted in the identification of possible inhibitors of mutant CDK4 proteins that bind the conformations induced by deleterious nsSNPs. Using computational prediction methods, we identified five nsSNPs as highly deleterious: R24C, Y180H, A205T, R210P, and R246C. From molecular docking and molecular dynamic studies, we observed that these deleterious nsSNPs affected CDK4-cyclin D1 and CDK4-flavopiridol interactions. Furthermore, in a virtual screening approach, the drug 5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDROXYPHENYL) _4H_CHROMEN_ 4_ONE displayed good binding affinity for proteins with the mutations R24C or R246C, the drug diosmin displayed good binding affinity for the protein with the mutation Y180H, and the drug rutin displayed good binding affinity for proteins with the mutations A205T and R210P. Overall, this computational investigation of the CDK4 gene highlights the link between genetic variation and biological phenomena in human cancer and aids in the discovery of molecularly targeted therapies for personalized treatment.

  11. Trophic Dynamics of Filter Feeding Bivalves in the Yangtze Estuarine Intertidal Marsh: Stable Isotope and Fatty Acid Analyses.

    PubMed

    Wang, Sikai; Jin, Binsong; Qin, Haiming; Sheng, Qiang; Wu, Jihua

    2015-01-01

    Benthic bivalves are important links between primary production and consumers, and are essential intermediates in the flow of energy through estuarine systems. However, information on the diet of filter feeding bivalves in estuarine ecosystems is uncertain, as estuarine waters contain particulate matter from a range of sources and as bivalves are opportunistic feeders. We surveyed bivalves at different distances from the creek mouth at the Yangtze estuarine marsh in winter and summer, and analyzed trophic dynamics using stable isotope (SI) and fatty acid (FA) techniques. Different bivalve species had different spatial distributions in the estuary. Glauconome chinensis mainly occurred in marshes near the creek mouth, while Sinonovacula constricta preferred the creek. Differences were found in the diets of different species. S. constricta consumed more diatoms and bacteria than G. chinensis, while G. chinensis assimilated more macrophyte material. FA markers showed that plants contributed the most (38.86 ± 4.25%) to particular organic matter (POM) in summer, while diatoms contributed the most (12.68 ± 1.17%) during winter. Diatoms made the largest contribution to the diet of S. constricta in both summer (24.73 ± 0.44%) and winter (25.51 ± 0.59%), and plants contributed no more than 4%. This inconsistency indicates seasonal changes in food availability and the active feeding habits of the bivalve. Similar FA profiles for S. constricta indicated that the bivalve had a similar diet composition at different sites, while different δ13C results suggested the diet was derived from different carbon sources (C4 plant Spartina alterniflora and C3 plant Phragmites australis and Scirpus mariqueter) at different sites. Species-specific and temporal and/or spatial variability in bivalve feeding may affect their ecological functions in intertidal marshes, which should be considered in the study of food webs and material flows in estuarine ecosystems.

  12. Trophic Dynamics of Filter Feeding Bivalves in the Yangtze Estuarine Intertidal Marsh: Stable Isotope and Fatty Acid Analyses

    PubMed Central

    Wang, Sikai; Jin, Binsong; Qin, Haiming; Sheng, Qiang; Wu, Jihua

    2015-01-01

    Benthic bivalves are important links between primary production and consumers, and are essential intermediates in the flow of energy through estuarine systems. However, information on the diet of filter feeding bivalves in estuarine ecosystems is uncertain, as estuarine waters contain particulate matter from a range of sources and as bivalves are opportunistic feeders. We surveyed bivalves at different distances from the creek mouth at the Yangtze estuarine marsh in winter and summer, and analyzed trophic dynamics using stable isotope (SI) and fatty acid (FA) techniques. Different bivalve species had different spatial distributions in the estuary. Glauconome chinensis mainly occurred in marshes near the creek mouth, while Sinonovacula constricta preferred the creek. Differences were found in the diets of different species. S. constricta consumed more diatoms and bacteria than G. chinensis, while G. chinensis assimilated more macrophyte material. FA markers showed that plants contributed the most (38.86 ± 4.25%) to particular organic matter (POM) in summer, while diatoms contributed the most (12.68 ± 1.17%) during winter. Diatoms made the largest contribution to the diet of S. constricta in both summer (24.73 ± 0.44%) and winter (25.51 ± 0.59%), and plants contributed no more than 4%. This inconsistency indicates seasonal changes in food availability and the active feeding habits of the bivalve. Similar FA profiles for S. constricta indicated that the bivalve had a similar diet composition at different sites, while different δ13C results suggested the diet was derived from different carbon sources (C4 plant Spartina alterniflora and C3 plant Phragmites australis and Scirpus mariqueter) at different sites. Species-specific and temporal and/or spatial variability in bivalve feeding may affect their ecological functions in intertidal marshes, which should be considered in the study of food webs and material flows in estuarine ecosystems. PMID:26261984

  13. HyPEP FY-07 Report: Initial Calculations of Component Sizes, Quasi-Static, and Dynamics Analyses

    SciTech Connect

    Chang Oh

    2007-07-01

    The Very High Temperature Gas-Cooled Reactor (VHTR) coupled to the High Temperature Steam Electrolysis (HTSE) process is one of two reference integrated systems being investigated by the U.S. Department of Energy and Idaho National Laboratory for the production of hydrogen. In this concept a VHTR outlet temperature of 900 °C provides thermal energy and high efficiency electricity for the electrolysis of steam in the HTSE process. In the second reference system the Sulfur Iodine (SI) process is coupled to the VHTR to produce hydrogen thermochemically. This report describes component sizing studies and control system strategies for achieving plant production and operability goals for these two reference systems. The optimal size and design condition for the intermediate heat exchanger, one of the most important components for integration of the VHTR and HTSE plants, was estimated using an analytic model. A partial load schedule and control system was designed for the integrated plant using a quasi-static simulation. Reactor stability for temperature perturbations in the hydrogen plant was investigated using both a simple analytic method and a dynamic simulation. Potential efficiency improvements over the VHTR/HTSE plant were investigated for an alternative design that directly couples a High Temperature Steam Rankin Cycle (HTRC) to the HTSE process. This work was done using the HYSYS code and results for the HTRC/HTSE system were compared to the VHTR/HTSE system. Integration of the VHTR with SI process plants was begun. Using the ASPEN plus code the efficiency was estimated. Finally, this report describes planning for the validation and verification of the HYPEP code.

  14. Computational analyses of transcriptomic data reveal the dynamic organization of the Escherichia coli chromosome under different conditions

    PubMed Central

    Ma, Qin; Yin, Yanbin; Schell, Mark A.; Zhang, Han; Li, Guojun; Xu, Ying

    2013-01-01

    The circular chromosome of Escherichia coli has been suggested to fold into a collection of sequentially consecutive domains, genes in each of which tend to be co-expressed. It has also been suggested that such domains, forming a partition of the genome, are dynamic with respect to the physiological conditions. However, little is known about which DNA segments of the E. coli genome form these domains and what determines the boundaries of these domain segments. We present a computational model here to partition the circular genome into consecutive segments, theoretically suggestive of the physically folded supercoiled domains, along with a method for predicting such domains under specified conditions. Our model is based on a hypothesis that the genome of E. coli is partitioned into a set of folding domains so that the total number of unfoldings of these domains in the folded chromosome is minimized, where a domain is unfolded when a biological pathway, consisting of genes encoded in this DNA segment, is being activated transcriptionally. Based on this hypothesis, we have predicted seven distinct sets of such domains along the E. coli genome for seven physiological conditions, namely exponential growth, stationary growth, anaerobiosis, heat shock, oxidative stress, nitrogen limitation and SOS responses. These predicted folding domains are highly stable statistically and are generally consistent with the experimental data of DNA binding sites of the nucleoid-associated proteins that assist the folding of these domains, as well as genome-scale protein occupancy profiles, hence supporting our proposed model. Our study established for the first time a strong link between a folded E. coli chromosomal structure and the encoded biological pathways and their activation frequencies. PMID:23599001

  15. Activation of microtubule dynamics increases neuronal growth via the nerve growth factor (NGF)- and Gαs-mediated signaling pathways.

    PubMed

    Sarma, Tulika; Koutsouris, Athanasia; Yu, Jiang Zhu; Krbanjevic, Aleksandar; Hope, Thomas J; Rasenick, Mark M

    2015-04-17

    Signals that activate the G protein Gαs and promote neuronal differentiation evoke Gαs internalization in rat pheochromocytoma (PC12) cells. These agents also significantly increase Gαs association with microtubules, resulting in an increase in microtubule dynamics because of the activation of tubulin GTPase by Gαs. To determine the function of Gαs/microtubule association in neuronal development, we used real-time trafficking of a GFP-Gαs fusion protein. GFP-Gαs concentrates at the distal end of the neurites in differentiated living PC12 cells as well as in cultured hippocampal neurons. Gαs translocates to specialized membrane compartments at tips of growing neurites. A dominant-negative Gα chimera that interferes with Gαs binding to tubulin and activation of tubulin GTPase attenuates neurite elongation and neurite number both in PC12 cells and primary hippocampal neurons. This effect is greatest on differentiation induced by activated Gαs. Together, these data suggest that activated Gαs translocates from the plasma membrane and, through interaction with tubulin/microtubules in the cytosol, is important for neurite formation, development, and outgrowth. Characterization of neuronal G protein dynamics and their contribution to microtubule dynamics is important for understanding the molecular mechanisms by which G protein-coupled receptor signaling orchestrates neuronal growth and differentiation.

  16. Classifying acoustic signals into phoneme categories: average and dyslexic readers make use of complex dynamical patterns and multifractal scaling properties of the speech signal

    PubMed Central

    2015-01-01

    Several competing aetiologies of developmental dyslexia suggest that the problems with acquiring literacy skills are causally entailed by low-level auditory and/or speech perception processes. The purpose of this study is to evaluate the diverging claims about the specific deficient peceptual processes under conditions of strong inference. Theoretically relevant acoustic features were extracted from a set of artificial speech stimuli that lie on a /bAk/-/dAk/ continuum. The features were tested on their ability to enable a simple classifier (Quadratic Discriminant Analysis) to reproduce the observed classification performance of average and dyslexic readers in a speech perception experiment. The ‘classical’ features examined were based on component process accounts of developmental dyslexia such as the supposed deficit in Envelope Rise Time detection and the deficit in the detection of rapid changes in the distribution of energy in the frequency spectrum (formant transitions). Studies examining these temporal processing deficit hypotheses do not employ measures that quantify the temporal dynamics of stimuli. It is shown that measures based on quantification of the dynamics of complex, interaction-dominant systems (Recurrence Quantification Analysis and the multifractal spectrum) enable QDA to classify the stimuli almost identically as observed in dyslexic and average reading participants. It seems unlikely that participants used any of the features that are traditionally associated with accounts of (impaired) speech perception. The nature of the variables quantifying the temporal dynamics of the speech stimuli imply that the classification of speech stimuli cannot be regarded as a linear aggregate of component processes that each parse the acoustic signal independent of one another, as is assumed by the ‘classical’ aetiologies of developmental dyslexia. It is suggested that the results imply that the differences in speech perception performance between

  17. Functional analyses in the milkweed bug Oncopeltus fasciatus (Hemiptera) support a role for Wnt signaling in body segmentation but not appendage development.

    PubMed

    Angelini, David R; Kaufman, Thomas C

    2005-07-15

    Specification of the proximal-distal (PD) axis of insect appendages is best understood in Drosophila melanogaster, where conserved signaling molecules encoded by the genes decapentaplegic (dpp) and wingless (wg) play key roles. However, the development of appendages from imaginal discs as in Drosophila is a derived state, while more basal insects produce appendages from embryonic limb buds. Therefore, the universality of the Drosophila limb PD axis specification mechanism has been debated since dpp expression in more basal insect species differs dramatically from Drosophila. Here, we test the function of Wnt signaling in the development of the milkweed bug Oncopeltus fasciatus, a species with the basal state of appendage development from limb buds. RNA interference of wg and pangolin (pan) produce defects in the germband and eyes, but not in the appendages. Distal-less and dachshund, two genes regulated by Wg signaling in Drosophila and expressed in specific PD domains along the limbs of both species, are expressed normally in the limbs of pan-depleted Oncopeltus embryos. Despite these apparently paradoxical results, Armadillo protein, the transducer of Wnt signaling, does not accumulate properly in the nuclei of cells in the legs of pan-depleted embryos. In contrast, engrailed RNAi in Oncopeltus produces cuticular and appendage defects similar to Drosophila. Therefore, our data suggest that Wg signaling is functionally conserved in the development of the germband, while it is not essential in the specification of the limb PD axis in Oncopeltus and perhaps basal insects.

  18. Dynamics of the interaction between cotton bollworm Helicoverpa armigera and nucleopolyhedrovirus as revealed by integrated transcriptomic and proteomic analyses.

    PubMed

    Xing, Longsheng; Yuan, Chuanfei; Wang, Manli; Lin, Zhe; Shen, Benchang; Hu, Zhihong; Zou, Zhen

    2017-04-12

    Over the past decades, Helicoverpa armigera nucleopolyhedrovirus (HearNPV) has been widely used for biocontrol of cotton bollworm, which is one of the most destructive pest insects in agriculture worldwide. However, the molecular mechanism underlying the interaction between HearNPV and host insects remains poorly understood. In this study, high throughput RNA-sequencing was integrated with label-free quantitative proteomics analysis to examine the dynamics of gene expression in the fat body of H. armigera larvae in response to challenge with HearNPV. RNA-sequencing-based transcriptomic analysis indicated that host gene expression was substantially altered, yielding 3,850 differentially expressed genes (DEGs), while no global transcriptional shut-off effects were observed in the fat body. Among the DEGs, 60 immunity-related genes were down-regulated after baculovirus infection, a finding that was consistent with the results of quantitative real-time RT-PCR (qRT-PCR). Gene ontology and functional classification demonstrated that the majority of down-regulated genes were enriched in gene cohorts involved in energy, carbohydrate, and amino acid metabolic pathways. Proteomics analysis identified differentially expressed proteins in the fat body, among which 76 were up-regulated, whereas 373 were significantly down-regulated upon infection. The down-regulated proteins are involved in metabolic pathways such as energy metabolism, carbohydrate metabolism (CM), and amino acid metabolism, in agreement with the RNA-seq data. Furthermore, correlation analysis suggested a strong association between the mRNA level and protein abundance in the H. armigera fat body. More importantly, the predicted gene interaction network indicated that a large subset of metabolic networks was significantly negatively regulated by viral infection, including CM-related enzymes such as aldolase, enolase, malate dehydrogenase, and triose-phosphate isomerase. Taken together, transcriptomic combined

  19. DYNAMICS OF EXTRACELLULAR SIGNAL-REGULATED KINASE (ERK) ACTIVATION IN DEVELOPING CEREBELLAR GRANULE CELLS (CGC): A SYSTEMS BIOLOGY-ORIENTED STUDY

    EPA Science Inventory

    The objective of this study was to 1) characterize the dynamics of ERK activation in response to BDNF and NMDA; 2) use computational models to promote understanding of the signaling network underlying ERK activation.

  20. Wnt signaling in skeletal muscle dynamics: myogenesis, neuromuscular synapse and fibrosis.

    PubMed

    Cisternas, Pedro; Henriquez, Juan P; Brandan, Enrique; Inestrosa, Nibaldo C

    2014-02-01

    The signaling pathways activated by Wnt ligands are related to a wide range of critical cell functions, such as cell division, migration, and synaptogenesis. Here, we summarize compelling evidence on the role of Wnt signaling on several features of skeletal muscle physiology. We briefly review the role of Wnt pathways on the formation of muscle fibers during prenatal and postnatal myogenesis, highlighting its role on the activation of stem cells of the adult muscles. We also discuss how Wnt signaling regulates the precise formation of neuromuscular synapses, by modulating the differentiation of presynaptic and postsynaptic components, particularly regarding the clustering of acetylcholine receptors on the muscle membrane. In addition, based on previous evidence showing that Wnt pathways are linked to several diseases, such as Alzheimer's and cancer, we address recent studies indicating that Wnt signaling plays a key role in skeletal muscle fibrosis, a disease characterized by an increase in the extracellular matrix components leading to failure in muscle regeneration, tissue disorganization and loss of muscle activity. In this context, we also discuss the possible cross-talk between the Wnt/β-catenin pathway with two other critical profibrotic pathways, transforming growth factor β and connective tissue growth factor, which are potent stimulators of the accumulation of connective tissue, an effect characteristic of the fibrotic condition. As it has emerged in other pathological conditions, we suggests that muscle fibrosis may be a consequence of alterations of Wnt signaling activity.

  1. Listen, follow me: Dynamic vocal signals of dominance predict emergent social rank in humans.

    PubMed

    Cheng, Joey T; Tracy, Jessica L; Ho, Simon; Henrich, Joseph

    2016-05-01

    Similar to the nonverbal signals shown by many nonhuman animals during aggressive conflicts, humans display a broad range of behavioral signals to advertise and augment their apparent size, strength, and fighting prowess when competing for social dominance. Favored by natural selection, these signals communicate the displayer's capacity and willingness to inflict harm, and increase responders' likelihood of detecting and establishing a rank asymmetry, and thus avoiding costly physical conflicts. Included among this suite of adaptations are vocal changes, which occur in a wide range of nonhuman animals (e.g., chimpanzees, rhesus monkeys) prior to aggression, but have not been systematically examined in humans. The present research tests whether and how humans use vocal pitch modulations to communicate information about their intention to dominate or submit. Results from Study 1 demonstrate that in the context of face-to-face group interactions, individuals spontaneously alter their vocal pitch in a manner consistent with rank signaling. Raising one's pitch early in the course of an interaction predicted lower emergent rank, whereas deepening one's pitch predicted higher emergent rank. Results from Study 2 provide causal evidence that these vocal shifts influence perceptions of rank and formidability. Together, findings suggest that humans use transient vocal changes to track, signal, and coordinate status relationships.

  2. Roles of proteome dynamics and cytokinin signaling in root to hypocotyl ratio changes induced by shading roots of Arabidopsis seedlings.

    PubMed

    Novák, Jan; Černý, Martin; Pavlů, Jaroslav; Zemánková, Jana; Skalák, Jan; Plačková, Lenka; Brzobohatý, Břetislav

    2015-05-01

    In nature, root systems of most terrestrial plants are protected from light exposure by growing in a dark soil environment. Hence, in vitro cultivation in transparent Petri dishes leads to physiological perturbations, but the mechanisms underlying root-mediated light perception and responses have not been fully elucidated. Thus, we compared Arabidopsis thaliana seedling development in transparent and darkened Petri dishes at low light intensity (20 µmol m(-2) s(-1)), allowing us to follow (inter alia) hypocotyl elongation, which is an excellent process for studying interactions of signals involved in the regulation of growth and developmental responses. To obtain insights into molecular events underlying differences in seedling growth under these two conditions, we employed liquid chromatography-mass spectrometry (LC-MS) shotgun proteomics (available via the PRIDE deposit PXD001612). In total, we quantified the relative abundances of peptides representing 1,209 proteins detected in all sample replicates of LC-MS analyses. Comparison of MS spectra after manual validation revealed 48 differentially expressed proteins. Functional classification, analysis of available gene expression data and literature searches revealed alterations associated with root illumination (inter alia) in autotrophic CO2 fixation, C compound and carbohydrate metabolism, and nitrogen metabolism. The results also indicate a previously unreported role for cytokinin plant hormones in the escape-tropism response to root illumination. We complemented these results with reverse transcription followed by quantitative PCR (RT-qPCR), chlorophyll fluorescence and detailed cytokinin signaling analyses, detecting in the latter a significant increase in the activity of the cytokinin two-component signaling cascade in roots and implicating the cytokinin receptor AHK3 as the major mediator of root to hypocotyl signaling in responses to root illumination.

  3. Structural dynamics of the cell nucleus: basis for morphology modulation of nuclear calcium signaling and gene transcription.

    PubMed

    Queisser, Gillian; Wiegert, Simon; Bading, Hilmar

    2011-01-01

    Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions. In neurons, intracellular calcium levels are controlled by ion channels in the plasma membrane such as NMDA receptors (NMDARs), voltage-gated calcium channels (VGCCs) and certain α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by calcium exchange pathways between the cytosol and internal calcium stores including the endoplasmic reticulum and mitochondria. Synaptic activity and the subsequent opening of ligand and/or voltage-gated calcium channels can initiate cytosolic calcium transients which propagate towards the cell soma and enter the nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope. We recently described the discovery that in hippocampal neurons the morphology of the nucleus affects the calcium dynamics within the nucleus. Here we propose that nuclear infoldings determine whether a nucleus functions as an integrator or detector of oscillating calcium signals. We outline possible ties between nuclear mophology and transcriptional activity and discuss the importance of extending the approach to whole cell calcium signal modeling in order to understand synapse-to-nucleus communication in healthy and dysfunctional neurons.

  4. Recruitment of Dynamic Endothelial Ca2+ Signals by the TRPA1 Channel Activator AITC in Rat Cerebral Arteries

    PubMed Central

    Qian, Xun; Francis, Michael; Solodushko, Viktoriya; Earley, Scott; Taylor, Mark S.

    2012-01-01

    Objective Stimulation of endothelial TRP channels, specifically TRPA1, promotes vasodilation of cerebral arteries through activation of Ca2+-dependent effectors along the myoendothelial interface. However, presumed TRPA1-triggered endothelial Ca2+ signals have not been described. We investigated whether TRPA1 activation induces specific spatial and temporal changes in Ca2+ signals along the intima that correlate with incremental vasodilation. Methods Confocal imaging, immunofluorescence staining and custom image analysis were employed. Results We found that endothelial cells of rat cerebral arteries exhibit widespread basal Ca2+ dynamics (44 ± 6 events/minute from 26 ± 3 distinct sites in a 3.6x104 μm2 field). The TRPA1 activator AITC increased Ca2+ signals in a concentration-dependent manner, soliciting new events at distinct sites. Origination of these new events corresponded spatially with TRPA1 densities in IEL holes, and the events were prevented by the TRPA1 inhibitor HC-030031. Concentration-dependent expansion of Ca2+ events in response to AITC correlated precisely with dilation of pressurized cerebral arteries (p = 0.93 by F-test). Correspondingly, AITC caused rapid endothelium-dependent suppression of asynchronous Ca2+ waves in subintimal smooth muscle. Conclusions Our findings indicate that factors that stimulate TRPA1 channels expand Ca2+ signal-effector coupling at discrete sites along the endothelium to evoke graded cerebral artery vasodilation. PMID:22928941

  5. Engineering light-inducible nuclear localization signals for precise spatiotemporal control of protein dynamics in living cells

    PubMed Central

    Niopek, Dominik; Benzinger, Dirk; Roensch, Julia; Draebing, Thomas; Wehler, Pierre; Eils, Roland; Di Ventura, Barbara

    2014-01-01

    The function of many eukaryotic proteins is regulated by highly dynamic changes in their nucleocytoplasmic distribution. The ability to precisely and reversibly control nuclear translocation would, therefore, allow dissecting and engineering cellular networks. Here we develop a genetically encoded, light-inducible nuclear localization signal (LINuS) based on the LOV2 domain of Avena sativa phototropin 1. LINuS is a small, versatile tag, customizable for different proteins and cell types. LINuS-mediated nuclear import is fast and reversible, and can be tuned at different levels, for instance, by introducing mutations that alter AsLOV2 domain photo-caging properties or by selecting nuclear localization signals (NLSs) of various strengths. We demonstrate the utility of LINuS in mammalian cells by controlling gene expression and entry into mitosis with blue light. PMID:25019686

  6. Injury-stimulated and self-restrained BMP signaling dynamically regulates stem cell pool size during Drosophila midgut regeneration.

    PubMed

    Tian, Aiguo; Wang, Bing; Jiang, Jin

    2017-03-13

    Many adult organs rely on resident stem cells to maintain homeostasis. Upon injury, stem cells increase proliferation, followed by lineage differentiation to replenish damaged cells. Whether stem cells also change division mode to transiently increase their population size as part of a regenerative program and, if so, what the underlying mechanism is have remained largely unexplored. Here we show that injury stimulates the production of two bone morphogenetic protein (BMP) ligands, Dpp and Gbb, which drive an expansion of intestinal stem cells (ISCs) by promoting their symmetric self-renewing division in Drosophila adult midgut. We find that BMP production in enterocytes is inhibited by BMP signaling itself, and that BMP autoinhibition is required for resetting ISC pool size to the homeostatic level after tissue repair. Our study suggests that dynamic BMP signaling controls ISC population size during midgut regeneration and reveals mechanisms that precisely control stem cell number in response to tissue needs.

  7. Engineering light-inducible nuclear localization signals for precise spatiotemporal control of protein dynamics in living cells.

    PubMed

    Niopek, Dominik; Benzinger, Dirk; Roensch, Julia; Draebing, Thomas; Wehler, Pierre; Eils, Roland; Di Ventura, Barbara

    2014-07-14

    The function of many eukaryotic proteins is regulated by highly dynamic changes in their nucleocytoplasmic distribution. The ability to precisely and reversibly control nuclear translocation would, therefore, allow dissecting and engineering cellular networks. Here we develop a genetically encoded, light-inducible nuclear localization signal (LINuS) based on the LOV2 domain of Avena sativa phototropin 1. LINuS is a small, versatile tag, customizable for different proteins and cell types. LINuS-mediated nuclear import is fast and reversible, and can be tuned at different levels, for instance, by introducing mutations that alter AsLOV2 domain photo-caging properties or by selecting nuclear localization signals (NLSs) of various strengths. We demonstrate the utility of LINuS in mammalian cells by controlling gene expression and entry into mitosis with blue light.

  8. The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus.

    PubMed

    Albers, H Elliott; Walton, James C; Gamble, Karen L; McNeill, John K; Hummer, Daniel L

    2017-01-01

    Virtually every neuron within the suprachiasmatic nucleus (SCN) communicates via GABAergic signaling. The extracellular levels of GABA within the SCN are determined by a complex interaction of synthesis and transport, as well as synaptic and non-synaptic release. The response to GABA is mediated by GABAA receptors that respond to both phasic and tonic GABA release and that can produce excitatory as well as inhibitory cellular responses. GABA also influences circadian control through the exclusively inhibitory effects of GABAB receptors. Both GABA and neuropeptide signaling occur within the SCN, although the functional consequences of the interactions of these signals are not well understood. This review considers the role of GABA in the circadian pacemaker, in the mechanisms responsible for the generation of circadian rhythms, in the ability of non-photic stimuli to reset the phase of the pacemaker, and in the ability of the day-night cycle to entrain the pacemaker.

  9. Non-monotonic dynamics and crosstalk in signaling pathways and their implications for pharmacology

    NASA Astrophysics Data System (ADS)

    van Wijk, Roeland; Tans, Sander J.; Wolde, Pieter Rein Ten; Mashaghi, Alireza

    2015-06-01

    Currently, drug discovery approaches commonly assume a monotonic dose-response relationship. However, the assumption of monotonicity is increasingly being challenged. Here we show that for two simple interacting linear signaling pathways that carry two different signals with different physiological responses, a non-monotonic input-output relation can arise with simple network topologies including coherent and incoherent feed-forward loops. We show that non-monotonicity of the response functions has severe implications for pharmacological treatment. Fundamental constraints are imposed on the effectiveness and toxicity of any drug independent of its chemical nature and selectivity due to the specific network structure.

  10. Revisiting the Nucleolus: From Marker to Dynamic Integrator of Cancer Signaling

    PubMed Central

    Ruggero, Davide

    2015-01-01

    Key signaling pathways (such as phosphoinositide 3-kinase, Myc, and RAS) act as sensors of energy, stress, and nutrient availability and integrate these inputs to directly control ribosomeproduction and gene expression at the translational level. This activity is normally directly coupled to cell growth, division, and survival. However, it remains poorly understood the extent to which changes in ribosome number and nucleolar integrity downstream of these key signaling pathways contribute to their oncogenic activity. Emerging studies provide interesting insight into how deregulations in RNA polymerase I activity may lead to tumorigenesis and suggest that new drugs targeting ribosomal DNA transcription may hold great promise for the treatment of cancer. PMID:22969157

  11. Dynamics of the Bingham Canyon mine landslides from long-period and short-period seismic signal analysis

    NASA Astrophysics Data System (ADS)

    Hibert, C.; Ekstrom, G.; Stark, C. P.

    2013-12-01

    On April 10, 2013, one of the largest landslides observed in North America occurred at the Bingham Canyon copper mine near Salt Lake City, Utah. Seismic waves recorded by the Global Seismographic Network suggest that two major slope failures occurred: at 03:31UT and at 05:06UT with long-period surface-wave magnitudes of Msw~5.1 and Msw~4.9 respectively. The combined debris of these landslides has been estimated at 150 million tonnes. We used long-period surface wave data to invert for the Landslide Force History (LFH) of each of the two events, allowing us to infer the trajectories of landslide motion and their average dynamic properties [1]. These inferred runout paths are broadly consistent with those deduced from analysis of the landslide scar using air photographs, satellite imagery and differential topographic maps. However, the total mass obtained from the LFH analysis is less consistent: using the observed runout distances for calibration [1], our inversions suggest a total landslide mass 50% less than that reported by the mining company. A further complexity, possibly related, is revealed by analysis of the short-period seismic waves, which indicates that the 05:06UT detection is in fact the composite signal of two distinct landslide seismic sources. Usually, high-frequency (HF, >1Hz) seismic signals generated by landslides are hard to observe because of their strong scattering and attenuation with distance. However, a very dense network of broadband seismic stations exists in the vicinity of the Bingham Canyon mine. Thus, we were able to compare the LFH, long-period and HF seismic signals for both events. Joint analysis of the inverted trajectory and the HF seismic signal recorded at the closest stations shows that, for the first 03:31UT event, a backward movement of the mass center started just after a final burst in the very high-frequency (VHF, >20Hz) signal. After this final burst, a tremor-like signal is observed in the VHF. This tremor-like signal

  12. The analysis of the influence of fractal structure of stimuli on fractal dynamics in fixational eye movements and EEG signal

    NASA Astrophysics Data System (ADS)

    Namazi, Hamidreza; Kulish, Vladimir V.; Akrami, Amin

    2016-05-01

    One of the major challenges in vision research is to analyze the effect of visual stimuli on human vision. However, no relationship has been yet discovered between the structure of the visual stimulus, and the structure of fixational eye movements. This study reveals the plasticity of human fixational eye movements in relation to the ‘complex’ visual stimulus. We demonstrated that the fractal temporal structure of visual dynamics shifts towards the fractal dynamics of the visual stimulus (image). The results showed that images with higher complexity (higher fractality) cause fixational eye movements with lower fractality. Considering the brain, as the main part of nervous system that is engaged in eye movements, we analyzed the governed Electroencephalogram (EEG) signal during fixation. We have found out that there is a coupling between fractality of image, EEG and fixational eye movements. The capability observed in this research can be further investigated and applied for treatment of different vision disorders.

  13. The analysis of the influence of fractal structure of stimuli on fractal dynamics in fixational eye movements and EEG signal

    PubMed Central

    Namazi, Hamidreza; Kulish, Vladimir V.; Akrami, Amin

    2016-01-01

    One of the major challenges in vision research is to analyze the effect of visual stimuli on human vision. However, no relationship has been yet discovered between the structure of the visual stimulus, and the structure of fixational eye movements. This study reveals the plasticity of human fixational eye movements in relation to the ‘complex’ visual stimulus. We demonstrated that the fractal temporal structure of visual dynamics shifts towards the fractal dynamics of the visual stimulus (image). The results showed that images with higher complexity (higher fractality) cause fixational eye movements with lower fractality. Considering the brain, as the main part of nervous system that is engaged in eye movements, we analyzed the governed Electroencephalogram (EEG) signal during fixation. We have found out that there is a coupling between fractality of image, EEG and fixational eye movements. The capability observed in this research can be further investigated and applied for treatment of different vision disorders. PMID:27217194

  14. Longitudinal Dynamic Analyses of Depression and Academic Achievement in the Hawaiian High Schools Health Survey using Contemporary Latent Variable Change Models

    PubMed Central

    McArdle, Jack; Hamagami, Fumiaki; Chang, Janice Y.; Hishinuma, Earl S.

    2014-01-01

    The scientific literature consistently supports a negative relationship between adolescent depression and educational achievement, but we are certainly less sure on the causal determinants for this robust association. In this paper we present multivariate data from a longitudinal cohort-sequential study of high school students in Hawai‘i (following McArdle, 2009; McArdle, Johnson, Hishinuma, Miyamoto, & Andrade, 2001). We first describe the full set of data on academic achievements and self-reported depression. We then carry out and present a progression of analyses in an effort to determine the accuracy, size, and direction of the dynamic relationships among depression and academic achievement, including gender and ethnic group differences. We apply three recently available forms of longitudinal data analysis: (1) Dealing with Incomplete Data -- We apply these methods to cohort-sequential data with relatively large blocks of data which are incomplete for a variety of reasons (Little & Rubin, 1987; McArdle & Hamagami, 1992). (2) Ordinal Measurement Models (Muthén & Muthén, 2006) -- We use a variety of statistical and psychometric measurement models, including ordinal measurement models to help clarify the strongest patterns of influence. (3) Dynamic Structural Equation Models (DSEMs; McArdle, 2009). We found the DSEM approach taken here was viable for a large amount of data, the assumption of an invariant metric over time was reasonable for ordinal estimates, and there were very few group differences in dynamic systems. We conclude that our dynamic evidence suggests that depression affects academic achievement, and not the other way around. We further discuss the methodological implications of the study. PMID:25598650

  15. A Markov chain method to determine the dynamic properties of compound extremes and their near future climate change signal

    NASA Astrophysics Data System (ADS)

    Sedlmeier, Katrin; Mieruch, Sebastian; Schädler, Gerd

    2014-05-01

    Compound extremes are receiving more and more attention in the scientific world because of their great impact on society. It is therefore of great interest how well state-of-the-art regional climate models can represent the dynamics of multivariate extremes. Furthermore, the near future climate change signal of compound extremes is interesting especially on the regional scale because high resolution information is needed for impact studies and mitigation and adaptation strategies. We use a method based on Markov Chains to assess these two questions. It is based on the representation of multivariate climate anomalies by first order Markov Chains. We partition our dataset into extreme and non-extreme regimes and reduce the multivariate dataset to a univariate time series which can then be described as a discrete stochastic process, a Markov Chain. From the transition matrix several descriptors such as persistence, recurrence time and entropy are derived which characterize the dynamic properties of the multivariate system. By comparing these descriptors for model and observation data, the representation of the dynamics of the climate system by different models is evaluated. Near future shifts or changes of the dynamics of compound extremes are detected by using regional climate projections and comparing the descriptors for different time periods. In order to obtain reliable estimates of a climate change signal, we use an ensemble of simulations to assess the uncertainty which arise in climate projections. Our work is based on an ensemble of high resolution (7 km) regional climate simulations for Central Europe with the COSMO-CLM regional climate model using different global driving data. The time periods considered are a control period (1971-200) and the near future (2021-2050) and running windows within these time periods. For comparison, E-Obs and HYRAS gridded observational datasets are used. The presentation will mainly focus on bivariate temperature and

  16. The cell envelope stress response of Bacillus subtilis: from static signaling devices to dynamic regulatory network.

    PubMed

    Radeck, Jara; Fritz, Georg; Mascher, Thorsten

    2017-02-01

    The cell envelope stress response (CESR) encompasses all regulatory events that enable a cell to protect the integrity of its envelope, an essential structure of any bacterial cell. The underlying signaling network is particularly well understood in the Gram-positive model organism Bacillus subtilis. It consists of a number of two-component systems (2CS) and extracytoplasmic function σ factors that together regulate the production of both specific resistance determinants and general mechanisms to protect the envelope against antimicrobial peptides targeting the biogenesis of the cell wall. Here, we summarize the current picture of the B. subtilis CESR network, from the initial identification of the corresponding signaling devices to unraveling their interdependence and the underlying regulatory hierarchy within the network. In the course of detailed mechanistic studies, a number of novel signaling features could be described for the 2CSs involved in mediating CESR. This includes a novel class of so-called intramembrane-sensing histidine kinases (IM-HKs), which-instead of acting as stress sensors themselves-are activated via interprotein signal transfer. Some of these IM-HKs are involved in sensing the flux of antibiotic resistance transporters, a unique mechanism of responding to extracellular antibiotic challenge.

  17. High-Dynamic-Range Fiber-Optic Link For Microwave Signals

    NASA Technical Reports Server (NTRS)

    Logan, Ronald T., Jr.; Lutes, George F.

    1992-01-01

    Ultrastable fiber-optic communications system transmits microwave signals between antenna sites of Deep Space Network (DSN) and central processing station several kilometers away. Permits relocation of critical components from front-end areas of DSN antennas to central location, permitting radio-frequency (RF) antenna arraying, improving DSN flexibility, maintainability, and system performance. Also useful in commercial analog and digital communications.

  18. Rapid Acquisition of Bias in Signal Detection: